I’m both sad and incredibly happy to read this. I lost my wife recently to a recurring metastatic melanoma. She was treated at MSK by an amazing team.

It was a terrifying diagnosis and literally would have been a guaranteed death sentence in 2017. In 2023, she had a very real chance of pulling through due to immunotherapy. Unfortunately some complications led to the worst outcome and we lost an amazing woman.

I remember that my wife said once that the everything she had on that journey was on the shoulders of those before. So maybe in some small way she helped with the research and a future mother, sister, wife, husband, son, dad will have hope where there was none.

I am a walking, talking, laughing, smiling result of the effects of immunotherapy. I was on Pembrolizumab on a six week cycle across eighteen months, administered at Charing Cross Hospital in London, after diagnosis in early 2022. It effectively dealt with my lung and brain cancer, with minimal side effects. This year, I returned to the gym and am sucking up every last opportunity to extract as much fun as I can with my wife. I am amongst the luckiest of souls, and feel deeply sorry for everyone who is losing to or has lost someone to cancer.

My sister was part of an immunotherapy trial years back. She was given weeks to live; the trial gave us years. Tailored medicine is truly a marvel.

Direct study link: https://www.sciencedirect.com/science/article/pii/S153561082...

> Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer

> CD40 agonism enhances antitumor immunity but is limited by systemic toxicity and poor efficacy. Here, we present a phase 1 study (NCT04059588) of intratumoral (i.t.) 2141-V11, an Fc-engineered anti-CD40 agonistic antibody with enhanced binding to the inhibitory receptor FcγRIIB. Among 12 metastatic cancer patients, 2141-V11 was well tolerated without dose-limiting toxicities. Six patients experienced tumor reduction, including two complete responses in melanoma and breast cancer. 2141-V11 induced regression in injected and non-injected lesions, correlating with systemic CD8+ T cell activation and mature tertiary lymphoid structures (TLSs) in complete responders. In CD40/FcγRs humanized mice bearing orthotopic tumors, i.t. 2141-V11 promoted de novo TLS formation, facilitating i.t. CD8+ T cell effector responses independent of lymph node priming. The resulting local immune responses by 2141-V11 mediated abscopal antitumor effects and sustained immune memory. These findings demonstrate that i.t. 2141-V11 is safe and promotes immune-privileged tumor microenvironments that promote systemic and durable antitumor immunity.

As a young person with Multiple Myeloma, these articles give me hope but I know a cure is a long way off.

I feel like I'm at the stage where Ill be one of the last people to die from it or I'll be one of the first to be cured of it.

I'm watching companies like Deepmind with great interest. It's my hope that these AI tools speeds up a cure before it's too late.

While promising, be VERY skeptical about efficacy claims of these early stage research drugs.

Tons of drugs in the pipeline that goes after these promising receptor targets. PD-1/PD-L1, CD47, CD40 (as mentioned in the article) etc. Keytruda (PD-1) is an incredible success both clinically and commercially, but there are many many other drugs buried in the clinical trial cemetery that initially showed promising results.

Medicine is really hard.

Can anyone comment on near term success of the prostate cancer trial? Asking for a friend.

> The findings have sparked a number of other clinical trials that the Ravetch lab is currently collaborating on with researchers at Memorial Sloan Kettering and Duke University. Now in either phase 1 or phase 2 study, the trials are investigating 2141-V11’s effect on specific cancers, including bladder cancer, prostate cancer, and glioblastoma—all aggressive and hard to treat. Collectively, nearly 200 people are enrolled in the studies.

Waiting for the Derek Lowe post, but... if this is legit, it's a 'holy flipping s**' moment. That kind of success in Phase I human trials is incredibly rare.

The fact that they were only testing a tiny group of patients (to make sure the treatment would not do more harm than good) with such astonishing remissions for two different very aggressive cancer types warms my heart.

Low toxicity, effective against many cancers, it's almost unbelievable.

If clinical success holds in phase 2 and 3, this is the next Keytruda.