Pfizer Presents Data from Phase 1b Trial Investigating Utomilumab (a 4-1BB agonist) in Combination with a Checkpoint Inhibitor

Excerpt:

“Pfizer Inc. PFE -0.26% today announced results from a Phase 1b trial of Pfizer’s investigational immunotherapy agent utomilumab (the proposed non-proprietary name for PF-05082566), a 4-1BB (also called CD137) agonist, in combination with pembrolizumab, a PD-1 inhibitor, in patients with advanced solid tumors. This is the first reported study of a 4-1BB agonist combined with a checkpoint inhibitor. Encouraging safety data from the study were shared today as an oral presentation at the 52 [nd] Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“ ‘While these are early data, the combination of utomilumab with pembrolizumab demonstrates an encouraging safety profile and an early indication of potential anti-tumor activity across solid tumors,’ said Anthony W. Tolcher, M.D., director of clinical research at South Texas Accelerated Research Therapeutics (START) San Antonio. ‘We believe these results warrant further investigation to confirm whether combining utomilumab with a checkpoint inhibitor may amplify anti-tumor responses.’ ”

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Immune System Cells from Tumors Might Control Cancer

Tumors contain immune system cells that attack cancer cells but are present in very small numbers, leading to the hope that a flood of these antitumor cells might eradicate cancer. This approach can work in melanomas, but has not yet worked against other kinds of cancers. Now, there’s a better way to concentrate antitumor immune system cells: they have a protein called CD137 on their surfaces; researchers recently used this distinction to extract these antitumor cells quickly and easily from both melanomas and ovarian cancer. The new study showed that peoples’ own antitumor cells recognized their tumors and that injections of these cancer fighting cells kept tumors from growing in mice. If other types of cancer also contain these antitumor immune system cells, this new approach could hold promise for treating a wide range of tumors.


CD137 Accurately Identifies and Enriches for Naturally-Occurring Tumor-Reactive T Cells in Tumor

“Purpose: Up-regulation of CD137 (4-1BB) on recently activated CD8+ T-cells has been used to identify rare viral or tumor antigen-specific T-cells from peripheral blood. Here, we evaluated the immunobiology of CD137 in human cancer and the utility of a CD137-positive separation methodology for the identification and enrichment of fresh tumor-reactive tumor-infiltrating lymphocytes (TILs) or tumor-associated lymphocytes (TAL) from ascites for use in adoptive immunotherapy. Experimental Design: TILs from resected ovarian cancer or melanoma were measured for surface CD137expression directly or after overnight incubation in the presence of tumor cells and homeostatic cytokines. CD137pos TILs were sorted and evaluated for anti-tumor activity in vitro and in vivo. Results: Fresh ovarian TILs and TALs naturally expressed higher levels of CD137 than circulating T-cells. An HLA-dependent increase in CD137 expression was observed following incubation of fresh enzyme-digested tumor or ascites in IL-7 and IL-15 cytokines, but not IL-2. Enriched CD137pos TILs, but not PD-1pos or PD-1neg CD137neg cells, possessed autologous tumor-reactivity in vitro and in vivo. In melanoma studies, all MART-1-specific CD8+ TILs up-regulated CD137 expression after incubation with HLA-matched, MART-expressing cancer cells and antigen-specific effector function was restricted to the CD137pos subset in vitro. CD137pos TILs also mediated superior anti-tumor effects in vivo, compared to CD137neg TILs. Conclusions: Our findings reveal a role for the TNFR-family member CD137 in the immunobiology of human cancer where it is preferentially expressed on tumor-reactive subset of TILs, thus rationalizing its agonistic engagement in vivo and its use in TIL selection for adoptive immunotherapy trials.”