Sri Krishna (Krish)

Neoantigen-specific tumor-infiltrating lymphocytes in gastrointestinal cancers: a phase 2 trial - Nature Medicine In an iterative phase 2 trial, patients with metastatic, treatment-refractory, mismatch repair proficient gastrointestinal cancers had responses to neoantigen-reactive tumor-infiltrating lymphocytes b...

NIH-research and NIH-funded research saves lives

www.nature.com/articles/s41...

Very cool study

Absolutely! It’s one of our major areas of interest including my labs :) the impetus is now on TIL in this space more than TCR tbh

Can’t speak for Iovance - I’m sure they gave multiple trials ongoing since the success of native TIL in melanoma- but in our branch we’re very much still working on old school expansion of native TIL (targeting neoag) in solid epithelial cancers.

The important conclusion is that bespoke TCR-T targeting private neoantigens CAN work (there was a prior study from PACT Biopharma with no responses). The goal is now to make this short term responses more durable. Lots of work ahead 3/3.

Several interesting correlates show up - most of the responses were in patients who have not received TIL targeting the same mutation, and targeting CD8 neoantigens. They were nevertheless not durable (unlike TIL in melanoma) 2/3

Adoptive transfer of personalized neoantigen-reactive TCR-transduced T cells in metastatic colorectal cancer: phase 2 trial interim results - Nature Medicine Preliminary findings in seven patients with mismatch repair-proficient metastatic colorectal cancer who were treated in the context of a phase 2 trial show that adoptive transfer of autologous periphe...

ICYMI - over the summer Maria Parkhurst from our branch published one of the first reports of clinical responses after adoptive cell transfer of TCR engineered private neoantigen (tumor mutation) targeting T cells in metastatic cancer patients 🧪🦠🔬🩺 1/3 #Immunosky
www.nature.com/articles/s41...

If it had an alternative initiation mutation even a driver p53 mutation is dispensable. we’ve seen a patient tumor responded to mutp53 T cells but then progressed with a wt p53 tumor (both tumors : initial and prog, had KRAS mut which is likely the driver) pretty mind boggling how much we don’t know

Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells Evaluation of a large panel of human cancer cells revealed that gain-of-function effects of mutant TP53 are not required for tumor growth and therapy resistance, whereas loss of wild-type TP53 functio...

GoF p53 mutations have been prevalent in the field but there’s a recent study that has challenged this notion - might be of interest: aacrjournals.org/cancerdiscov...

Thank you !

Hello Jon - pls add me to this list thank you !

Reposting this now that there’s more crowd here - it was lonely a year back 🧪🦠

Hello can I pls be added - figuring this out- thank you so much.

🩺🦠🧪🔬 #Immunosky #Scisky

We report that anti tumor T cells in the blood are very low in frequency, but are apparently less dysfunctional, more stem-like relative to the SAME T cell clones within the tumor. We were able to develop a gene signature of blood derived T cells and predict TCRs from the blood of patients.

Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic c... Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profili…

Can we find antitumor, neoantigenT cells and predict their TCRs in the blood of patients with metastatic solid tumors? How do their phenotypes compare to those within patient's tumor? We addressed these questions in our new Cancer_Cell study.

Thank you for the kind words 🙏🏽

Another day, another award for our branch chief Steve Rosenberg. This time, the Presidential National Medal of technology and innovation, for pioneering immunotherapy against cancer.
🧪🔬🦠🩺 #ImmunoSky
www.cancer.gov/news-events/...

As probably one of the few NIH researchers on here, I feel obligated to note that a US federal govt shutdown will also impact the approx 1500 clinical trials being conducted at the NIH, including those against cancer, Alzheimer's, and many other diseases. Hopefully it is averted. 🩺🦠🔬🧪

🧪🔬🦠🩺Pls share. We are evaluating postdoc candidates with interests computational or experimental immunology, or tumor biology, immunotherapy, T cell immunology, or genome engineering. ccr.cancer.gov/careers/post...

Here is the direct link to the postdoc positions: pls contact if interested here and elsewhere. ccr.cancer.gov/careers/post...

Hi Bluesky. I recently started my lab at the Surgery Branch, National Cancer Institute. We study T cell Immunology in human cancer patients with the goal of developing cell therapies. Pls share this, join us if you're interested! We are looking for postdocs! ccr.cancer.gov/staff-direct...