Tumor-targeted CD28 bispecific antibodies enhance the antitumor efficacy of PD-1 immunotherapy.

Monoclonal antibodies that block the programmed cell death 1 (PD-1) checkpoint have revolutionized cancer immunotherapy. However, many major tumor types remain unresponsive to anti-PD-1 therapy, and even among responsive tumor types, most of the patients do not develop durable antitumor immunity. It has been shown that bispecific antibodies activate T cells by cross-linking the TCR/CD3 complex with a tumor-specific antigen (TSA). The class of TSAxCD3 bispecific antibodies have generated exciting results in early clinical trials. We have recently described another class of "costimulatory bispecifics" that cross-link a TSA to CD28 (TSAxCD28) and cooperate with TSAxCD3 bispecifics. Here, we demonstrate that these TSAxCD28 bispecifics (one specific for prostate cancer and the other for epithelial tumors) can also synergize with the broader anti-PD-1 approach and endow responsiveness-as well as long-term immune memory-against tumors that otherwise do not respond to anti-PD-1 alone. Unlike CD28 superagonists, which broadly activate T cells and induce cytokine storm, TSAxCD28 bispecifics display little or no toxicity when used alone or in combination with a PD-1 blocker in genetically humanized immunocompetent mouse models or in primates and thus may provide a well-tolerated and "off the shelf" combination approach with PD-1 immunotherapy that can markedly enhance antitumor efficacy.

Undocumented African Immigrants' Experiences of HIV Testing and Linkage to Care.

In the United States, undocumented African immigrants living with HIV enter care late, potentially leading to adverse individual and population health outcomes, yet little is known about the specific experiences of HIV diagnosis and linkage to care among this population. We conducted individual, semi-structured interviews with adults who were undocumented African immigrants living with HIV in New York City. Interviews explored perspectives regarding individual, social, institutional, and societal barriers and facilitators of HIV testing and linkage to care. Of 14 participants from 9 different African countries, 9 were women and the median age was 44 years (interquartile range: 42-50). Participants described fear of discovery by immigration authorities as a substantial barrier to HIV testing and linking to initial medical appointments. Actual and perceived structural barriers to both testing and care linkage included difficulty obtaining health insurance and a belief that undocumented immigrants are ineligible for any health services. Participants also expressed reluctance to be tested because of HIV-related stigma within the immigrant communities that they heavily relied on. After diagnosis, however, participants overwhelmingly described a positive role of health and social service providers in facilitating linkage to HIV care. Concerns about immigration status and HIV-related stigma are significant barriers to HIV testing and linkage to care among undocumented African immigrants. Multilevel efforts to reduce stigma and increase awareness of available services could enhance rates of HIV testing and care linkage in this population.

Risk factors for Kaposi's sarcoma among HIV-positive individuals in a case control study in Cameroon.

BACKGROUND: Individuals co-infected with Kaposi's sarcoma herpesvirus (KSHV) and Human Immunodeficiency Virus (HIV) are at greatly increased risk of developing Kaposi's sarcoma (KS). The objective of the current analysis is to identify risk cofactors for KS among HIV-positive individuals. METHODS: We conducted a case-control study of KS in Cameroon on 161 HIV-positive and 14 HIV-negative cases and 680 HIV-positive and 322 HIV-negative controls. Participants answered a physician-administered questionnaire and provided blood and saliva specimens. Antibodies against KSHV lytic, K8.1, and latent, ORF73, antigens were measured by ELISA to determine KSHV serostatus. Conditional logistic regression was performed to determine multivariate odds ratios (OR) and 95% confidence intervals (CI) for risk factors associated with KS among HIV-positive cases and controls. RESULTS: Overall, 98% (158) of HIV-positive cases, 100% (14) of HIV-negative cases, 81% (550) of HIV-positive controls, and 80% (257) of HIV-negative controls were KSHV seropositive. Risk factors for KS among HIV-positive individuals included KSHV seropositivity (OR=9.6; 95% CI 2.9, 31.5), non-use of a mosquito bed net (OR 1.9; 95% CI 1.2, 2.9), minority ethnicity (OR=3.1; 95% CI 1.1, 9.3), treatment from a traditional healer (OR=2.3; 95% CI 1.5, 3.7), history of transfusion (OR=2.4; 95% CI 1.5, 3.9), and family history of cancer (OR=1.9; 95% CI 1.1, 3.1). CONCLUSION: KSHV seroprevalence of ≥80% indicates a high prevalence in the general population in Cameroon. Among HIV-positive individuals, the strong association of KS with non-use of mosquito nets and treatment from traditional healers are compelling findings, consistent with recently reported data from East Africa.