In vivo selection in non-human primates identifies AAV capsids for on-target CSF delivery to spinal cord.

Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal (IT) delivery of AAV vectors into cerebral spinal fluid can avoid many issues, although distribution of the vector throughout the spinal cord is limited, and vector entry to the periphery sometimes initiates hepatotoxicity. Here we performed biopanning in non-human primates (NHPs) with an IT injected AAV9 peptide display library. We identified top candidates by sequencing inserts of AAV DNA isolated from whole tissue, nuclei, or nuclei from transgene-expressing cells. These barcoded candidates were pooled with AAV9 and compared for biodistribution and transgene expression in spinal cord and liver of IT injected NHPs. Most candidates displayed increased retention in spinal cord compared with AAV9. Greater spread from the lumbar to the thoracic and cervical regions was observed for several capsids. Furthermore, several capsids displayed decreased biodistribution to the liver compared with AAV9, providing a high on-target/low off-target biodistribution. Finally, we tested top candidates in human spinal cord organoids and found them to outperform AAV9 in efficiency of transgene expression in neurons and astrocytes. These capsids have potential to serve as leading-edge delivery vehicles for spinal cord-directed gene therapies.

Evolution of a Continuing Professional Development Program Based on a Community of Practice Model for Health Care Professionals in Resource-Limited Settings.

INTRODUCTION: The Baylor International Pediatric AIDS Initiative (BIPAI) Network supports a network of independent nongovernmental organizations providing health care for children and families in low- and middle-income countries (LMIC). Using a community of practice (CoP) framework, a continuing professional development (CPD) program was created for health professionals to enhance knowledge and exchange best practices. METHODS: An online learning platform (Moodle), videoconferencing (Zoom), instant messaging systems (Whatsapp), and email listserv facilitated learning and interaction between program participants. Target participants initially included pharmacy staff and expanded to include other health professionals. Learning modules included asynchronous assignments and review of materials, live discussion sessions, and module pretests and posttests. Evaluation included participants' activities, changes in knowledge, and assignment completion. Participants provided feedback on program quality via surveys and interviews. RESULTS: Five of 11 participants in Year 1 earned a certificate of completion, and 17 of 45 participants earned a certificate in Year 2. Most modules showed an increase in module pretest and posttest scores. Ninety-seven percent of participants indicated that the relevance and usefulness of modules were good or outstanding. Ongoing evaluation indicated changes in Year 2 for program improvement, and notable outcomes indicated how CoP added value in developing a true community. DISCUSSION: Using a CoP framework allowed participants to improve their personal knowledge and become part of a learning community and network of interdisciplinary health care professionals. Lessons learned included expanding program evaluation to capture potential value creation of the community of practice in addition to individual-level development; providing briefer, more focused programs to better serve busy working professionals; and optimizing use of technological platforms to improve participant engagement.

Using starling murmuration as a model for creating a global health community of practice to advance equity in scholarship.

BACKGROUND: Disparities in scholarship exist between authors in low- or middle-income countries (LMIC) and high-income countries. Recognizing these disparities in our global network providing pediatric, adolescent, and maternal healthcare to vulnerable populations in LMIC, we sought to improve access and provide resources to address educational needs and ultimately impact the broader scholarship disparity. METHODS: We created a virtual community of practice (CoP) program underpinned by principles from starling murmuration to promote interdisciplinary scholarship. We developed guiding principles- autonomy, mastery and purpose- to direct the Global Health Scholarship Community of Practice Program. Program components included a continuing professional development (CPD) program, an online platform and resource center, a symposium for scholarship showcase, and peer coaching. RESULTS: From February 2021 to October 2022, 277 individuals joined. Eighty-seven percent came from LMIC, with 69% from Africa, 6% from South America, and 13% from other LMIC regions. An average of 30 members attended each of the 21 CPD sessions. Thirty-nine authors submitted nine manuscripts for publication. The symposium increased participation of individuals from LMIC and enhanced scholarly skills and capacity. Early outcomes indicate that members learned, shared, and collaborated as scholars using the online platform. CONCLUSION: Sharing of knowledge and collaboration globally are feasible through a virtual CoP and offer a benchmark for future sustainable solutions in healthcare capacity building. We recommend such model and virtual platform to promote healthcare education and mentoring across disciplines.

In vivo selection in non-human primates identifies superior AAV capsids for on-target CSF delivery to spinal cord.

Systemic administration of adeno-associated virus (AAV) vectors for spinal cord gene therapy has challenges including toxicity at high doses and pre-existing immunity that reduces efficacy. Intrathecal delivery of AAV vectors into the cerebral spinal fluid (CSF) can avoid many of the issues of systemic delivery, although achieving broad distribution of the vector and transgene expression throughout the spinal cord is challenging and vector entry to the periphery occurs, sometimes initiating hepatotoxicity. Here we performed two rounds of in vivo biopanning in non-human primates (NHPs) with an AAV9 peptide display library injected intrathecally and performed insert sequencing on DNA isolated from either whole tissue (conventional selection), isolated nuclei, or nuclei from transgene-expressing cells. A subsequent barcoded pool of candidates and AAV9 was compared at the DNA (biodistribution) and RNA (expression) level in spinal cord and liver of intrathecally injected NHPs. Most of the candidates displayed enhanced biodistribution compared to AAV9 at all levels of spinal cord ranging from 2 to 265-fold. Nuclear isolation or expression-based selection yielded 4 of 7 candidate capsids with enhanced transgene expression in spinal cord (up to 2.4-fold), while no capsid obtained by conventional selection achieved that level. Furthermore, several capsids displayed lower biodistribution to the liver of up to 1,250-fold, compared to AAV9, providing a remarkable on target/off target biodistribution ratio. These capsids may have potential for gene therapy programs directed at the spinal cord and the selection method described here should be useful in clinically relevant large animal models.

An Engineered Adeno-Associated Virus Capsid Mediates Efficient Transduction of Pericytes and Smooth Muscle Cells of the Brain Vasculature.

Neurodegeneration and cerebrovascular disease share an underlying microvascular dysfunction that may be remedied by selective transgene delivery. To date, limited options exist in which cellular components of the brain vasculature can be effectively targeted by viral vector therapeutics. In this study, we characterize the first engineered adeno-associated virus (AAV) capsid mediating high transduction of cerebral vascular pericytes and smooth muscle cells (SMCs). We performed two rounds of in vivo selection with an AAV capsid scaffold displaying a heptamer peptide library to isolate capsids that traffic to the brain after intravenous delivery. One identified capsid, termed AAV-PR, demonstrated high transduction of the brain vasculature, in contrast to the parental capsid, AAV9, which transduces mainly neurons and astrocytes. Further analysis using tissue clearing, volumetric rendering, and colocalization revealed that AAV-PR enabled high transduction of cerebral pericytes located on small-caliber vessels and SMCs in the larger arterioles and penetrating pial arteries. Analysis of tissues in the periphery indicated that AAV-PR also transduced SMCs in large vessels associated with the systemic vasculature. AAV-PR was also able to transduce primary human brain pericytes with higher efficiency than AAV9. Compared with previously published AAV capsids tropisms, AAV-PR represents the first capsid to allow for effective transduction of brain pericytes and SMCs and offers the possibility of genetically modulating these cell types in the context of neurodegeneration and other neurological diseases.

Realizing the Promise of Dolutegravir in Effectively Treating Children and Adolescents Living With HIV in Real-world Settings in 6 Countries in Eastern and Southern Africa.

BACKGROUND: Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs). METHODS: Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS). RESULTS: Among 9419 CALHIV using DTG, 7898 had a documented post-DTG VL, and VLS post-DTG was 93.4% (7378/7898). VLS for antiretroviral therapy (ART) initiations was 92.4% (246/263), and VLS was maintained for the ART-experienced [92.9% (7026/7560) pre- vs. 93.5% (7071/7560) post-DTG; P = 0.14). Among previously unsuppressed, 79.8% (426/534) achieved VLS with DTG. Only 5 patients reported a Grade 3 or 4 adverse event (0.057 per 100 patient-years) requiring DTG discontinuation. History of protease inhibitor-based ART [odds ratio (OR) = 1.53; 95% confidence interval (CI): 1.16-2.03], care in Tanzania (OR = 5.45; 95% CI: 3.41-8.70), and being 15-19 years old (OR = 1.31; 95% CI: 1.03-1.65) were associated with gain of VLS post-DTG. Predictors of VLS on DTG included VLS before DTG (OR = 3.87; 95% CI: 3.03-4.95) and using the once-daily, single tab tenofovir-lamivudine-DTG regimen (OR = 1.78; 95% CI: 1.43-2.22). SDS maintained VLS [95.9% (2032/2120) pre- vs. 95.0% (2014/2120) post-SDS with DTG; P = 0.19], and 83.0% (73/88) of unsuppressed gained VLS using SDS with DTG. CONCLUSIONS: We found DTG to be highly effective and safe within our cohort of CALHIV in LMICs. These findings can empower clinicians to prescribe DTG confidently to eligible CALHIV.

COVID-19 Impact on Disparity in Childhood Immunization in Low- and Middle-Income Countries Through the Lens of Historical Pandemics.

Purpose of Review: The COVID-19 pandemic, since 2020, has affected health care services and access globally. Although the entire impact of COVID-19 pandemic on existing global public health is yet to be fully seen, the impact of COVID-19 pandemic on global childhood immunization programs is of particular importance. Recent Findings: Disruptions to service delivery due to lockdowns, challenges in vaccination programs, vaccine misinformation and hesitancy, and political and social economic inequalities all posed a threat to existing childhood immunization programs. These potential threats were especially critical in LMIC where childhood immunization programs tend to experience suboptimal implementation. Summary: This review provides an overview of childhood immunizations and discusses past pandemics particularly in LMIC, factors contributing to disparities in childhood immunizations, and reviews potential lessons to be learned from past pandemics. Vaccine hesitancy, social determinants of health, and best practices to help lessen the pandemic's influence are also further elaborated. To address current challenges that hindered the progress made in prevention of childhood illnesses through vaccination campaigns and increased vaccine availability, lessons learned through best practices explored from past pandemics must be examined to mitigate impact of COVID-19 on childhood immunization and in turn conserve health and improve economic well-being of children especially in LMIC.

Disparities in Accessing Sexual and Reproductive Health Services and Rights Among Adolescents and Young People During COVID-19 Pandemic: Culture, Economic, and Gender Perspectives.

Purpose of Review: As the world grapples with the health systems' challenges during the COVID-19 pandemic, addressing the needs of the already vulnerable adolescents and young people is vital. This narrative synthesis is aimed to highlight the current gender, cultural, and socioeconomic dynamics fueling inequalities to accessing sexual, reproductive health and rights (SRHR) services among adolescents and young people in low- and middle-income countries (LMIC). Recent Findings: The COVID-19 pandemic has in most countries exacerbated already existing inequalities due to economic, gender, cultural, and legal aspects. Strategies implemented by most governments to mitigate the spread of the virus have also had a negative impact on the access to SRHR services, some of which are long term. Few published studies have assessed the extent to which the pandemic has fueled each of these paradigms regarding access to SRHR, especially among adolescents and young people (AYP). Additionally, there is paucity in data on the same in most countries, as the systems to track such effects were not available at the inception of the pandemic. Summary: Despite efforts to mitigate the effects of the pandemic on this population, deficits remain and a multi-stakeholder approach is needed to achieve the intended goals, especially where cultural and gender values are deeply rooted. Further research is needed to quantify how the pandemic has fueled economic, gender, and cultural aspects to influence access to SRHR services among AYP especially in LMIC.

Health Disparities in Children and Adolescents Living in LMIC During COVID-19 Pandemic.

Purpose of Review: The purpose of this editorial is to introduce the pediatric global health issue focusing on health disparities emerging from the COVID-19 pandemic on children and adolescents living in low- and middle-income countries (LMIC). Recent Findings: As the COVID-19 pandemic ensues, children and adolescents living in LMIC have been disproportionately affected by socio-economic and mitigation practices, leading to widening disparities in health and the social determinants of health that influence their well-being. Summary: This pediatric global health issue brings to bare the extent, range, and nature of these health disparities, integrated with expert viewpoints, to prompt critical dialogue to address these complex problems.

Global community of practice: A means for capacity and community strengthening for health professionals in low- and middle-income countries.

Background: Low- and middle-income countries face distinct challenges in providing health care services and training. The community of practice (CoP) has been described as a method of facilitating much-needed connections and conversations on this topic and has been adapted over time to include virtual CoPs. We describe the development and evaluation of a global Clinical Lead Forum (CLF) using a CoP framework to structure informal continuing professional development (CPD) and enhance the capacity of health care professionals in low- and middle-income countries. Methods: Baylor College of Medicine International Pediatric AIDS Initiative (BIPAI) and its network of affiliated, independent non-governmental organizations (NGOs) provide paediatric and maternal health care for vulnerable populations around the world. We established virtual sessions across the network to discuss clinical topics, which evolved based on the need to include a COVID-19 series. We collected demographic, participation, participant and facilitator assessments, as well as leadership notes from each session as part of an educational quality improvement study. We developed and evaluated the program using the Logic Model and used the Kirkpatrick Model to assess learning outcomes. Results: A total of 299 unique participants engaged in sessions, representing a total of 10 disciplines. There were a total of 1295 participants who joined for the 11 sessions in the regular CLF series and the 23 sessions in the COVID-19 series. Survey responses were overall consistent with a value-added intervention. Conclusions: The CLF, via both the regular sessions and the COVID-19 series, served as an impactful global health CoP for CPD. By focusing on creating a safe and inviting space, ensuring equity and inclusion, activating champions, fostering engagement, and promoting innovation and adaptability, this program decreased professional isolation, strengthened peer relationships, and enhanced the knowledge and practices of health care professionals. Our model may be scaled to other systems across the world to bridge divides and create similarly meaningful communities.

Achieving Antiretroviral Therapy Uptake and Viral Suppression Among Children and Adolescents Living With HIV in the UNAIDS 90-90-90 Era Across Six Countries in Eastern and Southern Africa-Lessons From the BIPAI Network.

BACKGROUND: Although achievements have been made globally since the UNAIDS 90-90-90 targets were announced, paediatric data remain sparse. We describe achievements toward antiretroviral therapy (ART) uptake and viral load (VL) suppression, existing gaps, and potential best practices among children and adolescents living with HIV (CALHIV) across 6 Eastern and Southern African countries. SETTING: Baylor College of Medicine International Paediatric AIDS Initiative Network sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania, and Uganda. METHODS: We performed retrospective data analysis among CALHIV ages 0-19 years between 2014 and 2019. RESULTS: A total of 25,370 CALHIV received care, 85.8% (21,773/25,370) received ART, 84.4% (18,376/21,773) had documented VL results, and 74.6% (13,715/18,376) had VL < 1000 cps/mL. By 2019, the pooled proportion of CALHIV receiving ART and having viral suppression increased to 99.8% [95% confidence interval (CI): 98.1 to 100.0] and 89.8% (95 CI: 88.2 to 91.5) respectively. Lower rates of viral suppression and higher lost to follow-up (LTFU) were seen in the 0-4-year and 15-19-year cohorts. CALHIV on ART not achieving viral suppression were younger, received care in Malawi or Mbeya, had a history of tuberculosis, lower rates of integrase-strand inhibitor-based ART, and were on ART for shorter durations. Best practices reported included adopting universal ART, ART optimization with protease inhibitor-based and/or dolutegravir-based regimens, peer-supported activities, child/adolescent friendly services, community-supported activities, and technology-driven quality improvement activities and digital solutions. CONCLUSIONS: High rates of CALHIV receiving ART and having viral suppression can be achieved in settings in Eastern and Southern Africa through using pediatric best practices. Increased efforts must be made to address LTFU and to support under-fives and adolescents.

The cancer-testis antigen, sperm protein 17, a new biomarker and immunological target in head and neck squamous cell carcinoma.

Head and Neck Squamous Cell Carcinoma is a deadly and locally aggressive malignancy that frequently portends a poor prognosis. Since current treatment modalities including surgery, chemotherapy and radiation are heavily debilitating and often result in recurrence intense efforts have been put into the development of novel less toxic and more lasting treatment strategies. Recently, immunotherapy has been proposed as a promising alternative that could potentially meet these requirements. SP17 is a validated cancer-testis antigen in multiple myeloma, ovarian cancer and non-small cell lung cancer. We aim at studying SP17 expression in HNSCC and its immunogenicity as a possible future target for HNSCC therapeutic vaccines. SP17 expression was evaluated in tissue specimens of HNSCC patients and controls. Moreover, SP17 immunogenicity was studied by generating autologous dendritic cells in vitro from the peripheral blood mononucleated cells of HNSCC patients and testing their ability to induce SP17 specific cytotoxic lymphocytes capable of killing autologous tumor cells in vitro. SP17specific immune responses were also evaluated in HNSCC patients as circulating anti-SP17 autoantibodies. SP17 was expressed in HNSCC tissues of HNSCC patients. Autologous dendritic cells pulsed with SP17 antigen induced powerful SP17 MHC class-I restricted, perforin-dependent, cytotoxic T-cells capable of efficiently killing autologous tumor cells in vitro. SP17-specific autoantibodies were detectable in the serum of HNSCC patients irrespective of tumor site or TNM stage. In conclusion, SP17 is an ideal immunotherapeutic target for HNSCC and a potential serological biomarker of the disease.

Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy.

Breast carcinoma is a major health issue for millions of women. Current therapies have serious side effects, and are only partially effective in patients with metastatic tumors. Thus, the need for novel and less toxic therapies is urgent. Moreover, hormonal and antibody therapies effective in other subtypes are not effective in Triple Negative Breast Cancer (TNBC). Immunotherapeutic strategies directed against specific tumor-associated antigens (TAAs) and mediated by specific cytotoxic T lymphocytes (CTL) have been largely underexplored in this disease. Cancer-testis antigens (CTA) are a group of TAAs displaying the ideal characteristics of promising vaccine targets, i.e. strong immunogenicity and cancer specificity. The CTA, Sperm Protein 17 (SP17), has been found to be aberrantly expressed in different neoplasms, including ovarian and esophageal cancers, nervous system tumors and multiple myeloma, and has been suggested as a candidate target for immunotherapy. Here, we evaluated SP17 expression levels in breast cancer cell lines, invasive ductal breast carcinoma, including patients with TNBC, and adjacent non-neoplastic breast tissue, and determined whether SP17 was capable of generating SP17-specific cytotoxic T lymphocytes in vitro. We showed that SP17 is expressed in breast cancer cell lines and primary breast tumors and importantly in TNBC subtype, but not in adjacent non-tumoral breast tissue or unaffected tissues, except in male germinal cells. Furthermore, we detected specific anti-SP17 antibodies in patients' sera and we generated SP17-specific, HLA class I-restricted, cytotoxic T lymphocytes capable of efficiently killing breast cancer cells.

Addressing health disparities in Hispanic breast cancer: accurate and inexpensive sequencing of BRCA1 and BRCA2.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes account for 20-25 % of inherited breast cancers and about 10 % of all breast cancer cases. Detection of BRCA mutation carriers can lead to therapeutic interventions such as mastectomy, oophorectomy, hormonal prevention therapy, improved screening, and targeted therapies such as PARP-inhibition. We estimate that African Americans and Hispanics are 4-5 times less likely to receive BRCA screening, despite having similar mutation frequencies as non-Jewish Caucasians, who have higher breast cancer mortality. To begin addressing this health disparity, we initiated a nationwide trial of BRCA testing of Latin American women with breast cancer. Patients were recruited through community organizations, clinics, public events, and by mail and Internet. Subjects completed the consent process and questionnaire, and provided a saliva sample by mail or in person. DNA from 120 subjects was used to sequence the entirety of BRCA1 and BRCA2 coding regions and splice sites, and validate pathogenic mutations, with a total material cost of $85/subject. Subjects ranged in age from 23 to 81 years (mean age, 51 years), 6 % had bilateral disease, 57 % were ER/PR+, 23 % HER2+, and 17 % had triple-negative disease. RESULTS: A total of seven different predicted deleterious mutations were identified, one newly described and the rest rare. In addition, four variants of unknown effect were found. CONCLUSIONS: Application of this strategy on a larger scale could lead to improved cancer care of minority and underserved populations.

Galectins in cancer: carcinogenesis, diagnosis and therapy.

A major breakthrough in the field of medical oncology has been the discovery of galectins and their role in cancer development, progression and metastasis. In this review article we have condensed the results of a number of studies published over the past decade in an effort to shed some light on the unique role played by the galectin family of proteins in neoplasia, and how this knowledge may alter the approach to cancer diagnosis as well as therapy in the future. In this review we have also emphasized the potential use of galectin inhibitors or modulators in the treatment of cancer and how this novel treatment modality may affect patient outcomes in the future. Based on current pre-clinical models we believe the use of galectin inhibitors/modulators will play a significant role in cancer treatment in the future. Early clinical studies are underway to evaluate the utility of these promising agents in cancer patients.

Galectin-3 inhibition suppresses drug resistance, motility, invasion and angiogenic potential in ovarian cancer.

OBJECTIVE: Ovarian cancer is the most deadly gynecologic malignancy worldwide. Since the pathogenesis of ovarian cancer is incompletely understood, and there are no available screening techniques for early detection, most patients are diagnosed with advanced, incurable disease. In an effort to develop innovative and effective therapies for ovarian cancer, we tested the effectiveness of Galecti-3C in vitro. This is a truncated, dominant negative form of Galectin-3, which is thought to act by blocking endogenous Galectin-3. METHODS: We produced a truncated, dominant-negative form of Galectin-3, namely Galetic-3C. Ovarian cancer cell lines and primary cells from ovarian cancer patients were treated with Galectin-3C, and growth, drug sensitivity, and angiogenesis were tested. RESULT: We show, for the first time, that Galectin-3C significantly reduces the growth, motility, invasion, and angiogenic potential of cultured OC cell lines and primary cells established from OC patients. CONCLUSIONS: Our findings indicate that Galectin-3C is a promising new compound for the treatment of ovarian cancer.

The role of human papilloma virus (HPV) infection in non-anogenital cancer and the promise of immunotherapy: a review.

Over the past 30 years, human papilloma virus (HPV) has been shown to play a role in the development of various cancers. Most notably, HPV has been linked to malignant progression in neoplasms of the anogenital region. However, high-risk HPV has also been suggested to play a significant role in the development of cancers in other anatomic locations, such as the head and neck, lung, breast and bladder. In 2006, the first vaccine for HPV, Gardasil, was approved for the prevention of subtypes 6, 11, 16 and 18. A few years later, Cevarix was approved for the prevention of subtypes 16 and 18, the HPV subtypes most frequently implicated in malignant progression. Although increased awareness and vaccination could drastically decrease the incidence of HPV-positive cancers, these approaches do not benefit patients who have already contracted HPV and developed cancer as a result. For this reason, researchers need to continue developing treatment modalities, such as targeted immunotherapies, for HPV-positive lesions. Here, we review the potential evidence linking HPV infection with the development of non-anogenital cancers and the potential role of immunotherapy in the prevention and eradication of HPV infection and its oncogenic sequela.

Anti-galectin-3 therapy: a new chance for multiple myeloma and ovarian cancer?

Here we review the role of Galectins in the molecular pathogenesis of multiple myeloma and ovarian cancer, with a special focus on Glectin-3. Multiple myeloma is the second most common hematologic malignancy worldwide. Because the pathogenesis of multiple myeloma is still incompletely understood, there is no ultimately effective cure, and this cancer results fatal. Ovarian cancer is the most lethal gynecologic malignancy worldwide. Due to the lack of screening techniques for early detection, patients are mostly diagnosed with advanced disease, which results ultimately fatal. Multiple myeloma and ovarian cancer have different biologies, but they share a strong dependence on adhesion with extracellular matrix and other cells. Galectin-3 plays a key role in regulating such adhesive abilities of tumor cells. Here we discuss the outcomes and possible mechanism of action of a truncated, dominant negative form of Galectin-3, Galectin-3C, in these malignancies. Overall, we report that Galectin-3C is a promising new compound for effective adjuvant therapies in advanced, refractory multiple myeloma and ovarian cancer.