The Center for Immunology brings together clinicians and scientists seeking to develop innovative new strategies for harnessing the immune system in the fight against human cancers. The immune system is designed to quell the spread of viruses and other microbial pathogens. In cancer, the challenge is that malignant cells are often not seen as foreign or dangerous, and thus avoid elimination by the immune system. While the past decade has witnessed remarkable progress in our ability to leverage the immune system in the war on cancer, these successes have been limited to a few major human malignancies (for example, melanoma, non-small cell lung cancer, kidney cancer). These cancers are ‘visible’ to the immune system either because of the burden of mutations they accumulate, or because the microenvironment of these tumors make such cancers immunologically inflamed, or ‘hot’. Disappointingly, the vast majority of human cancers resist immune-based therapies. The Center for Immunology maintains that immunotherapy of all human cancers can greatly improved if we learn how to render immunologically cold tumors hot, and seeks to do so by exploiting the strengths of its scientists and clinicians in several areas of basic and translational immunology.
We are particularly keen on partnering with pharmaceutical companies for conceptually novel proof-of-principle and efficacy biomarker (phase 0) validation trials based on patient samples to advance their new therapeutic agents to the clinic.
Below are some examples of prior or current immunotherapy-related clinical trials written and designed by our Investigators.
Combination of Interferon-gamma and Nivolumab for Advanced Solid Tumors (NCT02614456)
Matthew Zibelman, MD
Phase I study of combination immunotherapy with IFN-γ and the PD-1 inhibitor nivolumab in patients with advanced solid tumors who have progressed on at least one prior systemic therapy, which may include prior immunotherapy. Completed accrual. Results demonstrated that the combination was safe, with modest efficacy but including one durable complete response. Relative paucity of immune related adverse events investigated and hypothesized to be related to interferon-gamma. Published in Nature Communications.
A Phase 2, Open-label Study of Pembrolizumab Monotherapy in Patients With Metastatic High Grade Neuroendocrine Tumors (NCT02939651)
Namrata Vijayvergia, MD
This single-arm, phase two study investigated the role of pembrolizumab in high grade neuroendocrine tumors in patients after progression on platinum-based chemotherapy. Efficacy was found to be limited. Translational work showed that high baseline peripheral T-cell count and reduced activation of T and NK cell subsets was associated with improved outcomes. High post-treatment TIGIT and TIM-3 expression suggested possible mechanisms of resistance. Results published in British Journal of Cancer and Cancer Immunology, Immunotherapy.
MEL-212: A Phase I Proof-of-Concept Study of CBL0137 (Curaxin) Combined With Ipilimumab and Nivolumab Therapy in Locally Advanced or Metastatic Melanoma (NCT05498792)
Anthony Olszanski, MD, RPh
This phase I, single-arm, window-of-opportunity safety study is evaluating the addition of CBL0137 (Curaxin) in patients with locally advanced or metastatic melanoma getting immunotherapy with ipilimumab and nivolumab. The trial intends to establish the safety of adding curaxin to this established combination, as well as investigating whether the addition of curaxin leads to changes in the tumor microenvironment causing release of tumor antigens optimizing the potential for an immune response. The scientific premise for this was published in Nature from the lab of Siddharth Balachandran. This trial is currently accruing patients.