ALT-803, a complex of an interleukin-15 (IL-15) superagonist mutant and a dimeric IL-15 receptor α/Fc fusion protein, was found to exhibit significantly stronger in vivo biological activity on NK and T cells than IL-15. In this study, we show that a single dose of ALT-803, but not IL-15 alone, eliminated well-established 5T33P and MOPC-315P myeloma cells in the bone marrow of tumor-bearing mice. ALT-803 treatment also significantly prolonged survival of myeloma-bearing mice and provided resistance to rechallenge with the same tumor cells through a CD8+ T cell-dependent mechanism. ALT-803 treatment stimulated CD8+ T cells to secrete large amounts of interferon-γ (IFN-γ) and promoted rapid expansion of CD8+CD44high memory T cells in vivo. These memory CD8+ T cells exhibited ALT-803-mediated up-regulation of NKG2D (KLRK1) but not PD-1 (PDCD1) or CD25 (IL2RA) on their cell surfaces. ALT-803-activated CD8+ memory T cells also exhibited non-specific cytotoxicity against myeloma and other tumor cells in vitro, whereas IFN-γ had no direct effect on myeloma cell growth. ALT-803 lost its anti-myeloma activity in tumor-bearing IFN-γ knockout mice but retained the ability to promote CD8+CD44high memory T cell proliferation, indicating that ALT-803-mediated stimulation of CD8+CD44high memory T cells is IFN-γ-independent. Thus, besides well-known IL-15 biological functions in host immunity, this study demonstrates that IL-15-based ALT-803 could activate CD8+CD44high memory T cells to acquire a unique innate-like phenotype and secrete IFN-γ for non-specific tumor cell killing. This unique immune modulatory property of ALT-803 strongly supports its clinical development as a novel immunotherapeutic agent against cancer and viral infections.

Faculty of color experience a number of challenges within academia, including tokenism, marginalization, racial microaggressions, and a disconnect between their racial/ethnic culture and the culture within academia. The present study examined epistemic exclusion as another challenge in which formal institutional systems of evaluation combine with individual biases toward faculty of color to devalue their scholarship and deem them illegitimate as scholars. Using data from interviews with 118 faculty of color from a single predominantly White, research-intensive institution, we found that epistemic exclusion occurs through formal hierarchies that determine how scholarship is valued and the metrics used to assess quality, and through informal processes that further convey to faculty of color that they and their scholarship are devalued. In addition, there was variability in reporting these experiences by race, gender, nationality, and discipline. We found that faculty of color coped with epistemic exclusion by being assertive and by seeking validation and support outside the institution. Finally, participants described a number of negative work-related and psychological consequences of their epistemic exclusion. We discuss epistemic exclusion as a form of academic gatekeeping that impedes the recruitment, advancement, and retention of faculty of color and offer strategies to address this barrier.

Although intersectionality has become part of the everyday lexicon, the field of psychology has demonstrated resistance to the theory, which we argue reflects epistemic exclusion. Epistemic exclusion is the devaluation of some scholarship as illegitimate and certain scholars as lacking credibility. We suggest that intersectionality has been epistemically excluded because it challenges dominant psychological norms about the scientific process and has been most readily endorsed by psychologists from marginalized groups. We provide evidence that epistemic exclusion has occurred through formal means (e.g., exclusion from mainstream journals) and informal processes (e.g., repeated misrepresentation of the theory). We use visibility theory to highlight the role of disciplinary power in this process, such that dominant psychologists act as gatekeepers. Finally, we discuss how the epistemic exclusion of intersectionality is a barrier to social issues scholarship and social justice in psychology, and offer structural recommendations for intersectionality's epistemic inclusion. Psychologists' awareness of intersectionality continues to grow as the tenets of the theory and the term itself form part of the everyday lexicon. Nevertheless, intersectionality scholars maintain

IL15 induces the activation and proliferation of natural killer (NK) and memory CD8 T cells and has preclinical antitumor activity. Given the superior activity and favorable kinetics of ALT-803 (IL15N72D:IL15RαSu/IgG1 Fc complex) over recombinant human IL15 (rhIL15) in animal models, we performed this first-in-human phase I trial of ALT-803 in patients with advanced solid tumors. Patients with incurable advanced melanoma, renal cell, non-small cell lung, and head and neck cancer were treated with ALT-803 0.3 to 6 μg/kg weekly intravenously or 6 to 20 μg/kg weekly subcutaneously for 4 consecutive weeks, every 6 weeks. Immune correlates included pharmacokinetics, immunogenicity, and lymphocyte expansion and function. Clinical endpoints were toxicity and antitumor activity. Twenty-four patients were enrolled; 11 received intravenous and 13 received subcutaneous ALT-803. Of these patients, nine had melanoma, six renal, three head and neck, and six lung cancer. Although total lymphocyte and CD8 T-cell expansion were modest, NK cell numbers rose significantly. Neither anti-ALT-803 antibodies nor clinical activity were observed. Overall, ALT-803 was well tolerated, with adverse effects including fatigue and nausea most commonly with intravenous administration, whereas painful injection site wheal was reported most commonly with subcutaneous ALT-803. Subcutaneous ALT-803 produced the expected NK cell expansion and was well tolerated with minimal cytokine toxicities and a strong local inflammatory reaction at injection sites in patients with advanced cancer. These data, together with compelling evidence of synergy in preclinical and clinical studies, provide the rationale for combining ALT-803 with other anticancer agents. .