HN Reader

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.

Funded primarily by US taxpayers via 6 NIH grants from the National Cancer Institute and NCATS, with additional support from private foundations including the Robertson Fund, V Foundation for Cancer Research, Breast Cancer Alliance, and Beckman Foundation.

The day after tomorrow I am driving 12 hours across three states to get my dog the second shot of his immunotherapy treatment for hemangiosarcoma. It’s only available in trial (this is a yale study). Results for him are too early, but the standard prognosis with chemo is 3-6 months.

This feels like we are on the cusp of profound medical breakthroughs treatment of cancer. My thanks to everyone who contributes to this kind of medical and scientific progress.

My wife had Crohn's disease since a teenager, and was diagnosed with metastatic gallbladder cancer aged 52. A death sentence. She chose to do aggressive chemo to prolong her life from a few weeks to a few months. She suffered a great deal before she died.

An immunotherapy treatment was discussed, and it could possibly have helped a lot, but it carried a somewhat high risk of causing a disastrous Crohn's flare that would kill her immediately. The doctor was unwilling to try this because it might kill her. So she died inevitably without it.

It was a classic medical ethics case right there in our crisis. We did a lot of interesting and intense things in those months before she died. Fuck.

One of the hugely important takeaways of this study is that even though the therapy was applied at the site of the most significant tumor, the immune response appeared to trigger against presumably ALL tumors throughout the body.

> “The melanoma patient had dozens of metastatic tumors on her leg and foot, and we injected just one tumor up on her thigh,” Ravetch says. “After multiple injections of that one tumor, all the other tumors disappeared. The same thing happened in the patient with metastatic breast cancer, who also had tumors in her skin, liver, and lung. And even though we only injected the skin tumor, we saw all the tumors disappear.”

Bring it faster, I beg you.

This is a good development. Who's going to have access to this medication if it comes to market? Will it be for the wealthy or will the poor have access to it?

If all tumors would randomly grow or shrink, then half of the tumors will shrink indeed.

My mother is currently battling stage 4 GBM. We are trying out a an immunotherapy vaccine developed Germany. It's still in trials and doesn't cure anything, but if it prolongs her life that would be the best case scenario, so we took the chance.

Really hoping to see a breakthrough in immunotherapy drugs in the next few years.

Related topic: http://timesofindia.indiatimes.com/life-style/health-fitness...

Claims today of "100% Efficacy Vaccine"

Out of 12, only 6 saw their tumor shrink and 2 were tumor free.

Thats 17% saw a complete response, 33% a partial response and 50% no response.

It’s not particularly striking results, though any progress is welcome.

University press releases aren’t exactly the most unbiased sources of scientific information.