Advanced stage cancers annihilated by activating CD40 antibody treatment

In a significant breakthrough for cancer research, a new treatment approach has shown promising results in a Phase I clinical trial. The trial, led by Jeffrey V. Ravetch's lab at Memorial Sloan Kettering and Duke University, focused on an enhanced CD40 agonistic antibody called 2141.V11.

The trial, published in Cancer Cell, included 12 metastatic cancer patients. Six patients experienced systemic tumor reduction, with two achieving complete response (cancer disappearance). The two patients whose cancer disappeared had a high clonality of T cells at the start of the study.

The researchers injected 2141.V11 directly into tumors instead of intravenously to minimize toxic side effects. This approach allowed the drug to stimulate immune activity at the tumor site, as revealed by tissue samples that showed the presence of tertiary lymphoid structures (TLS). The presence of TLS is associated with improved prognosis and response to immunotherapy.

CD40 is a cell surface receptor and member of the tumor necrosis factor (TNF) receptor superfamily of proteins, predominantly expressed on antigen-presenting cells such as dendritic cells, B cells, and macrophages. When triggered by binding to its ligand, CD40 prompts the immune system to spring into action, initiating antitumor immunity and developing tumor-specific T cell responses.

The effect of 2141.V11 wasn't limited to tumors that were directly injected; it also affected tumors elsewhere in the body. This systemic response is a promising development, as it suggests that the drug could potentially treat cancer in its entirety, not just the injected tumor.

The trial findings have sparked a number of other clinical trials investigating 2141-V11's effect on specific cancers, including bladder cancer, prostate cancer, and glioblastoma. Nearly 200 people are enrolled in these studies to help understand why some patients respond to 2140-V11 and others do not.

This development is particularly significant given that a class of anticancer drugs called CD40 agonist antibodies has shown limited impact on patients in clinical trials. The biggest challenge in the field is to determine which patients will benefit from immunotherapy and how to convert non-responders into responders.

2141.V11 proved to be 10 times more powerful in its capacity to elicit an antitumor immune response compared to previous CD40 agonist antibodies. This enhanced efficacy, combined with the reduced systemic toxicity, makes 2141.V11 a promising candidate for further investigation in the fight against metastatic cancer.

The report is titled "Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer." The findings suggest that 2141.V11 could be a game-changer in the field of cancer treatment, offering a new approach to stimulating the immune system to combat cancer.