IL-18-secreting multiantigen targeting CAR T cells eliminate antigen-low myeloma in an immunocompetent mouse model.

ABSTRACT: Multiple myeloma is a plasma cell malignancy that is currently incurable with conventional therapies. Following the success of CD19-targeted chimeric antigen receptor (CAR) T cells in leukemia and lymphoma, CAR T cells targeting B-cell maturation antigen (BCMA) more recently demonstrated impressive activity in relapsed and refractory myeloma patients. However, BCMA-directed therapy can fail due to weak expression of BCMA on myeloma cells, suggesting that novel approaches to better address this antigen-low disease may improve patient outcomes. We hypothesized that engineered secretion of the proinflammatory cytokine interleukin-18 (IL-18) and multiantigen targeting could improve CAR T-cell activity against BCMA-low myeloma. In a syngeneic murine model of myeloma, CAR T cells targeting the myeloma-associated antigens BCMA and B-cell activating factor receptor (BAFF-R) failed to eliminate myeloma when these antigens were weakly expressed, whereas IL-18-secreting CAR T cells targeting these antigens promoted myeloma clearance. IL-18-secreting CAR T cells developed an effector-like T-cell phenotype, promoted interferon-gamma production, reprogrammed the myeloma bone marrow microenvironment through type-I/II interferon signaling, and activated macrophages to mediate antimyeloma activity. Simultaneous targeting of weakly-expressed BCMA and BAFF-R with dual-CAR T cells enhanced T-cell:target-cell avidity, increased overall CAR signal strength, and stimulated antimyeloma activity. Dual-antigen targeting augmented CAR T-cell secretion of engineered IL-18 and facilitated elimination of larger myeloma burdens in vivo. Our results demonstrate that combination of engineered IL-18 secretion and multiantigen targeting can eliminate myeloma with weak antigen expression through distinct mechanisms.

HIV Nursing.

These nurses provide compassionate care to patients with HIV and AIDS.

Detecting HIV among persons accompanying patients to an infectious diseases clinic.

BACKGROUND: Infectious diseases (ID) clinics are locations where members of at risk social networks, including sex partners of HIV-infected patients, make contact with a medical care setting when they accompany HIV-positive patients to appointments. METHODS: We implemented a free point-of-care rapid HIV testing program for anyone accompanying a patient to the University of North Carolina ID clinic. Acceptability of the program among the general clinic population was assessed via an anonymous survey 1 year after program implementation. Basic frequencies of those who underwent and received results of rapid HIV testing, the proportion of positive rapid tests and confirmatory HIV tests performed, and the level of University of North Carolina ID clinic patient satisfaction with the HIV testing program were calculated. RESULTS: Between October 2007 and June 2013, 450 (99.6%) of 452 individuals tested in the program received their results on the same day as testing. Twenty-two individuals (4.9%) tested HIV positive, of which 16 (72.7%) were newly positive, including 3 never previously tested. Excluding previously diagnosed individuals, HIV prevalence was 3.6% (16/446). Among those testing positive by rapid testing, 19 (86.4%) had confirmatory testing and immediately entered into HIV care at the clinic. CONCLUSIONS: The high positivity and confirmatory HIV rates in our program confirm that the provision of rapid HIV testing in an ID clinic capitalizes on missed opportunities among an at-risk population and allows immediate linkage to care.

Experiences with HIV testing, entry, and engagement in care by HIV-infected women of color, and the need for autonomy, competency, and relatedness.

Self-determination theory examines the needs of people adopting new behaviors but has not been applied to the adoption of HIV healthcare behaviors. The current study applied self-determination theory to descriptions of healthcare behaviors adopted by ethnic minority women after an HIV diagnosis. Women of color were asked to describe their experiences with HIV testing, entry, and engagement-in-care in qualitative interviews and focus groups. Participants were mostly African-American (88%), over 40 years old (70%), had been diagnosed for more than 6 years (87%) and had disclosed their HIV infection to more than 3 people (73%). Women described unmet self-determination needs at different time points along the HIV Continuum of Care. Women experienced a significant loss of autonomy at the time of HIV diagnosis. Meeting competency and relatedness needs assisted women in entry and engagement-in-care. However, re-establishing autonomy was a key element for long-term engagement-in-care. Interventions that satisfy these needs at the optimal time point in care could improve diagnosis, entry-to-care, and retention-in-care for women living with HIV.