Memgen biopharmaceutical recently presented a poster, entitled “Induction of Potent Systemic Anti-Melanoma Immunity through Intratumoral CD40 Activation and Checkpoint Blockade,” describing the positive results of Memgen’s lead product, ISF35, in preclinical studies with mice carrying B16 melanomas, a well-established and widely used mouse model for human melanoma. The results of the preclinical studies, led by Willem Overwijk, PhD, and Manisha Singh, PhD, at The University of Texas MD Anderson Cancer Center in Houston, were presented at the 30th Annual Meeting of the Society of Immunotherapy of Cancer (SITC) in National Harbor, Maryland.
ISF35 is a first-in-class, T-cell cancer immunotherapy that promotes an anti-tumor immune response. Its anti-tumor action can be further enhanced by combining ISF35 with immune checkpoint inhibitors, increasing the drug’s mode of action to other types of tumor, including lung cancer, metastatic melanoma, and hepatocellular carcinoma.
In the preclinical studies recently presented, researchers at Memgen administered ISF35 directly into the mouse melanoma tumor (intratumor injection), which induced an anti-tumor immune response mediated by key CD8+ T cells (cytotoxic T cells). Notably, the anti-tumor action generated targeted the injected tumor as well as distal non-injected tumors in mice, inhibiting growth and triggering regression. When combined with anti-PD-1 immune checkpoint inhibitor therapy, anti-tumoral response was enhanced; and in a combination therapy of ISF35/anti-PD-1/anti-CTLA-4, researchers detected a complete regression of melanomas in approximately 50% of the mice, which was accompanied by production of memory CD8 T-cell responses (a small population of specific T cells that retain memory for fighting a detrimental cell if they encounter it again).
Mark Cantwell, PhD, President of Memgen and co-inventor of ISF35, said in a press release: “There have been significant advances in the survival and treatment of many cancer types with immune-oncology (IO) drugs, primarily as monotherapy with checkpoint inhibitors. With the next wave of clinical development aiming to find the right combinations of IO drugs that improve patient outcomes while still keeping a tolerable safety profile, the preclinical results provide strong support that ISF35 in combination with checkpoint inhibitors can achieve this goal.
“We look forward to soon beginning a phase I/II clinical trial of ISF35 and Keytruda (pembrolizumab) in refractory metastatic melanoma. This trial will be an important step in identifying synergistic combinations that will enhance checkpoint immunotherapies.”