Complement regulators as novel targets for anti-cancer therapy: A comprehensive review.

Cancer remains a formidable global health challenge requiring the continued exploration of innovative therapeutic approaches. While traditional treatment strategies including surgery, chemotherapy, and radiation therapy have had some success, primarily in early-stage disease, the quest for more targeted, personalized, safer, and effective therapies remains an ongoing pursuit. Over the past decade, significant advances in the field of tumor immunology have dramatically shifted a focus towards immunotherapy, although the ability to harness and coopt the immune system to treat cancer is still just beginning to be realized.

Complement factor H targeting antibody GT103 in refractory non-small cell lung cancer: a phase 1b dose escalation trial.

GT103 is a first-in-class, fully human, IgG3 monoclonal antibody targeting complement factor H that kills tumor cells and promotes anti-cancer immunity in preclinical models. We conducted a first-in-human phase 1b study dose escalation trial of GT103 in refractory non-small cell lung cancer to assess the safety of GT103 (NCT04314089). Dose escalation was performed using a "3 + 3" schema with primary objectives of determining safety, tolerability, PK profile and maximum tolerated dose (MTD) of GT103.

Complement factor H: a novel innate immune checkpoint in cancer immunotherapy.

The elimination of cancer cells critically depends on the immune system. However, cancers have evolved a variety of defense mechanisms to evade immune monitoring, leading to tumor progression. Complement factor H (CFH), predominately known for its function in inhibiting the alternative pathway of the complement system, has recently been identified as an important innate immunological checkpoint in cancer.

Perspective: rethinking therapeutic strategies in oncology.

Immuno-oncology has revolutionized cancer care, drug development, the design of clinical trials, standard treatment paradigms, and the evaluation of response to therapy. These are all areas, however, that have not fully incorporated principles of tumor immunology. Insufficient emphasis is put on the effect drugs have on the immune system, and specifically, the impact that multiple lines of therapy can have on the functioning of the immune system, hindering a robust anti-tumor immune response.