GigaGen Publishes Research Describing Potential New Avenues to Overcome Resistance to anti-PD-L1 Therapies

South San Francisco, Calif., May 25, 2021 (GLOBE NEWSWIRE) -- GigaGen Inc., a biotechnology company advancing transformative antibody drugs for infectious diseases, transplant rejection and checkpoint resistant cancers, and a subsidiary of Grifols, announced today publication of research, titled, “Single cell transcriptomics reveals the effect of PD-L1/TGF-β blockade on the tumor microenvironment,” in the peer-reviewed journal BMC Biology. The preclinical data describes potential new avenues to overcome resistance to anti-PD-L1 therapies.

“A major goal in oncology is to find strategies that enhance the infiltration of immune T cells in the tumor to improve efficacy of therapies, while reducing resistance and toxic effects,” said Erica Stone, Ph.D., vice president of Oncology at GigaGen and author of the study. “Our preclinical data shed light on the molecular mechanisms of existing cancer immunotherapies, such as anti-PD-L1 and/or anti-TGF-β therapy, and hints at potential new targets and novel therapeutic approaches for overcoming resistance to anti-PD-L1 oncology therapies.”

David Johnson, Ph.D., co-founder and chief executive officer of GigaGen, added, “Our team continues to make great progress at characterizing diverse drug resistance mechanisms and translating our findings into a pipeline of novel drug candidates with differentiated anti-tumor mechanisms. In addition to our bi-specific anti-PD-L1 x anti-TGF- β antibody, which enhances immune cell infiltration into the tumor, we are advancing a third generation anti-CTLA-4 monoclonal antibody, GIGA-564. GIGA-564 is designed to regulate immune response specifically in the tumor microenvironment, with potential to provide superior efficacy and reduced toxicity.”

Using GigaGen’s Magnify platform, the study evaluated molecular changes at the single cell level within the tumor microenvironment in a preclinical cancer model after treatment with anti-PD-L1 and/or anti-TGF-β. The analysis was complemented with in vivo testing to evaluate the potential antitumor activity of a newly discovered target, chemokine CCL5.

Key study highlights include:

• PD-L1 and/or TGF-β blockade led to an increased expression of genes responsible for recruiting cytotoxic lymphocytes (immune cells involved in tumor destruction) including multiple chemokines such as CCL5
• PD-L1 and TGF-β blockade led to reduction of proteins that contribute to the formation of an extracellular matrix around the tumor which impedes the infiltration of immune cells in the tumor
• The therapeutic delivery of a chemokine in in vivo mouse models increased infiltration of cytotoxic lymphocytes in the tumor and, in combination with anti-PD-L1, reduction of tumor size
• The data highlights the therapeutic potential of CCL5 plus anti-PD-L1 treatment