Cell-based cancer immunotherapy, such as chimeric antigen receptor (CAR) engineered T and natural killer (NK) cell therapies, has become a revolutionary new pillar in cancer treatment. Interleukin 15 (IL-15), a potent immunostimulatory cytokine that potentiates T and NK cell immune responses, has demonstrated the reliability and potency to potentially improve the therapeutic efficacy of current cell therapy. Structurally similar to interleukin 2 (IL-2), IL-15 supports the persistence of CD8⁺ memory T cells while inhibiting IL-2-induced T cell death that better maintains long-term anti-tumor immunity. In this review, we describe the biology of IL-15, studies on administrating IL-15 and/or its derivatives as immunotherapeutic agents, and IL-15-armored immune cells in adoptive cell therapy. We also discuss the advantages and challenges of incorporating IL-15 in cell-based immunotherapy and provide directions for future investigation.

Gamma delta (γδ) T cells are a minor population of T cells that share adaptive and innate immune properties. In contrast to MHC-restricted alpha beta (αβ) T cells, γδ T cells are activated in an MHC-independent manner, making them ideal candidates for developing allogeneic, off-the-shelf cell-based immunotherapies. As the field of cancer immunotherapy progresses rapidly, different subsets of γδ T cells have been explored. In addition, γδ T cells can be engineered using different gene editing technologies that augment their tumor recognition abilities and antitumor functions. In this review, we outline the unique features of different subsets of human γδ T cells and their antitumor properties. We also summarize the past and the ongoing pre-clinical studies and clinical trials utilizing γδ T cell-based cancer immunotherapy.

No current academic data is available with respect to the optimal timing to initiate antiretroviral therapy (ART) in HIV-positive patients with talaromycosis. Our study aimed to evaluate the optimal timing of ART initiation for patients presenting with AIDS-related talaromycosis. In this prospective, randomized, open-label multicenter trial, 228 patients from 15 hospitals in China were randomly assigned to an early ART group (initiation of ART within 2 weeks after randomization) and a deferred ART group (initiation of ART 2 weeks after randomization). The primary endpoint was all-cause mortality during the 48 weeks after randomization. We observed a significant difference in mortality between the early ART group and the deferred ART group (2.2% vs. 8.9%, 95%CI: -0.15 to 14.05, p = 0.049). The composite outcome of AIDS-defining events or death in the early ART group was found to be lower than that in the deferred ART group (3.3% vs. 14.9%; 95%CI: 2.93 to 19.23, p = 0.008). The prognosis of HIV-infected patients with talaromycosis in the early ART group was more favorable than that of patients in the deferred ART group. These results demonstrate that early ART initiation should be considered in HIV-infected patients with talaromycosis .

TPS669 Background: A substantial number of breast cancer survivors who are taking aromatase inhibitors (AIs) complain of side effects including arthralgias. Given the efficacy of AIs, it is essential that we identify approaches to mitigate arthralgias. We are conducting an NCI-funded trial is to examine the impact of a year-long exercise intervention in 180 breast cancer survivors taking an AI and experiencing at least mild arthralgias. Outcomes include severity of arthralgias, endocrine-related quality of life, % body fat, bone mass, and serum markers of inflammation. The purpose of this abstract is to present preliminary recruitment and adherence results. Methods: Women are being recruited via the Connecticut Tumor Registry and Rapid Case Ascertainment Shared Resource of Yale Cancer Center into the Hormones and Physical Exercise (HOPE) Study. Participants are randomly assigned to exercise (n = 90) or usual care (n = 90). The exercise intervention includes supervised resistance and unsupervised aerobic exercise sessions over 12 months. Data are collected at baseline, 3-, 6-, 9 and 12-months. Results: Study recruitment began in April 2010 and will continue through December 2012. As of January 1, 2012, we have received 1605 names of potentially eligible women. Of these 1605, 777 women are waiting to be screened (e.g., letter mailed to patient or on hold because recently diagnosed), 244 women could not be screened (e.g., unable to contact by phone), and 584 women have completed a telephone screening. Of the 584 women screened, 24% were ineligible because of discontinuing AIs because of arthralgias or chose not to take AIs primarily because of this potential side effect; another 36% were ineligible for various reasons; 24% were not interested; 11% were randomized (n = 65 women); and 5% are undergoing baseline visits (n = 29). On average, women are 62 yrs old and have been taking an AI for 1.8 yrs. Twenty-three women have completed the trial, with high exercise adherence rates (attendance to supervised sessions = 82% ). Conclusions: A growing number of women are choosing to not take AIs or are discontinuing AIs because of side effects. Our study may prove beneficial for the growing number of women diagnosed with hormone receptor-positive breast cancer each year.