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 lost my wife before they developed sickle cell treatments recently. Knowing the pain she went through everyday, makes me grateful that children soon will not have to know that pain. Thank you for sharing your story.
Having lost my mother to melanoma over 20 years ago, it is very encouraging to see the progress that has been made against this terrible disease. Very sorry for your loss.
I’m so sorry for your loss and thank you for sharing your wife’s story. As a husband, father, and son starting treatment for melanoma tomorrow, your words mean a lot. It’s humbling to think of how much today’s progress is owed to courage of those who came before
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 mother had immunotherapy treatment last year for lung cancer. It caused a lethal arrhythmia within 24 hours that they could not treat. She was dead by the end of that day. The cardiologist said this was a known side effect (he muttered 5% as she lay there). It's still not a perfect solution.
To be fair, not knowing your mother's age or cancer, 5% is right around the mortality rate for major surgery in the elderly too. Things are just dangerous as you approach end of life and there are no good solutions for anything.
What are the odds of chemo sucking every moment of joy out of your life and then you die anyway.
I think I could deal with 20:1 odds if I had a clean before and after. Tell everyone you love them, hope to see them soon, then take your 95% chance of having an extra few years.
> 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.
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.
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.
Readit News
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.
Very true and profound, I'm sorry for you loss, what an inspirational thing to say.
Deleted Comment
10 years ago, this wasn't an option. 5 or so years ago it wasn't a treatment for her cancer (metastatic renal).
I'm so thankful this treatment is available and that the genetic testing lined up.
I think I could deal with 20:1 odds if I had a clean before and after. Tell everyone you love them, hope to see them soon, then take your 95% chance of having an extra few years.
That said, we all know that these are not perfect solutions. They save some more, they don't save all.
Him and his wife committed hard to tons of clinical trials and is still alive to this day and has no indication he’ll be dying anytime soon.
He’s the very first patient on a number of studies, which he thinks is pretty cool.
> 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.
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.
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.
Mot many that showed such dramatic results across different types of cancer with very low toxicity.
Even if it turns out this drug kills 10% of patients outright, it would still be useful.
Deleted Comment
> 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.
[0] https://www.science.org/blogs/pipeline
Deleted Comment