Holy moly, this is an incredible paper!

For more than two decades, researchers have chased a powerful idea: harnessing CD40, a receptor that can flip on the immune system’s cancer-fighting power. Early drugs failed. They triggered dangerous side effects and delivered little benefit. 

Now, a new study from Dr. Jeffrey Ravetch at Rockefeller University and funded by the V Foundation has changed the story. Dr. Ravetch and team re-engineered a CD40 antibody, 2141-V11, and tested it by injecting it directly into tumors. The result?

• In a phase 1 trial, 6 of 12 patients with advanced cancers saw their tumors shrink!

• Two patients; one with melanoma and one with breast cancer, had their tumors disappear completely!!!

• Even tumors that weren’t injected shrank, showing a rare and dramatic systemic immune response!

Here’s the science behind these incredible results: the drug sparked the growth of tertiary lymphoid structures (TLSs) inside tumors. Think of TLSs as mini-immune training camps where immune cells learn to recognize and attack cancer cells. 

And here’s an analogy to help explain the outcomes: earlier CD40 drugs were like turning on all the lights in a house at once and risking blowing the fuse (toxicity). This new approach flips the light on only in the ‘tumor room’, but once the immune system sees what’s inside, it learns how to patrol the whole house. Bingo! Brilliant!

This is the kind of high-risk, high-reward research that donors to the V Foundation make possible. By investing in bold, innovative science, we help turn “what if” into clinical breakthroughs. 

I LOVE this paper! And, it’s not just progress, it’s proof that persistence and innovation can change the trajectory for patients who have run out of options. 

Find the Ravetch lab here The Rockefeller University » Jeffrey V. Ravetch and read this awesome paper at Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer - ScienceDirect.