#Neoantigens
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nature.com
Nature research paper: Tumour-wide RNA splicing aberrations generate actionable public neoantigens

https://go.nature.com/4hTQ0UW
Tumour-wide RNA splicing aberrations generate actionable public neoantigens - Nature
A study identifies public neoantigens generated by tumor-wide aberrant mRNA splicing activity across distinct cancer types.
go.nature.com
February 24, 2025 at 11:06 AM
c0nc0rdance.bsky.social
A paradox of cancer:
The most dangerous tumor types are the ones that look the least like cancer.

In technical terms: low expression of 'neoantigens' (mutant proteins) allows early tumors to evade your immune system.

Vaccine-induced immune response to a tumor's neoantigens could reverse that.
peiferlabunc.bsky.social Mark Peifer (He, him) @peiferlabunc.bsky.social · May 13
While BioNtech & Moderna become household names because of their Covid vaccines, those emerged from different projects: finding ways to treat the most challenging cancers. They hypothesized that we could vaccinate patients against their own tumors, & evidence is mounting that they were right! 1/n 🧪
https://www.nature.com/articles/s41586-025-10004-2 Individualized mRNA vaccines evoke durable T cell immunity in adjuvant TNBC U. Sahin, M. Schmidt, E. Derhovanessian, A. Cortini, I. Vogler, T. Omokoko, E. Godehardt, S. Attig, S. Newrzela, J. Grützner, N. Bidmon, S. Bolte, S. Brachtendorf, T. Stuhlmann, D. Langer, D. Brüne, J. Blake, A. Feldner, H. Lindman, A. Schneeweiss, M. Eichbaum & Ö. Türeci Triple-negative breast cancer (TNBC) is frequently associated with metastatic relapse, even at an early stage1. Here we assessed an individualized neoantigen mRNA vaccine in 14 patients with TNBC following surgery and after neoadjuvant or adjuvant therapy. In peripheral blood of nearly all patients, high-magnitude, vaccine-induced, mostly de novo T cell responses to multiple neoantigens were detected that remained functional for several years. Characterization of individual patients revealed that a large proportion of these T cells developed into two subsets: a late-differentiated phenotype with markers indicative of ‘ready-to-act’ cytotoxic effector T cells, and T cells with a stem cell-like memory phenotype. Eleven patients remained relapse-free for up to six years post-vaccination. Recurrence occurred in three patients: the individual with the weakest vaccine-induced T cell response relapsed, but achieved complete remission on subsequent anti-PD-1 therapy; another patient had a tumour with low major histocompatibility complex (MHC) class I expression with MHC class I-deficient cells growing out under vaccination; and the third patient was BRCA-positive and had a recurrence from a genetically distinct primary tumour. These findings demonstrate the feasibility of individualized RNA vaccines in TNBC, document persistence of vaccine-induced, functional neoantigen-specific T cells and provide insights into possible immune escape mechanisms that will guide future approaches.
May 13, 2026 at 11:45 AM
science.org
A new generation of cancer-preventing vaccines could wipe out tumors before they form.

Learn more on #WorldCancerDay: https://scim.ag/4gk8Qmo
Preventive cancer vaccines deliver tumor antigens or neoantigens, so that the immune system will attack tumor cells.
February 4, 2025 at 7:56 PM
johannajoyce.bsky.social
Vaccines can elicit long-lived immune activity against #pancreatic #cancer

Sethna et al, MSKCC, report that personalized vaccines encoding neoantigens can induce durable CD8+ T cell responses- correlating w/ better long-term outcomes 🧪⚕️

www.nature.com/articles/s41...
www.nature.com/articles/d41...
February 20, 2025 at 9:28 PM
shihcheng.bsky.social
Tumor-wide RNA splicing errors create neoantigens across various cancers, boosting T-cell immunotherapies! Limited mutations, massive potential. #Neoantigens PMID:39972144, Nature 2025, @Nature https://doi.org/10.1038/s41586-024-08552-0 #Medsky #Pharmsky #RNA 🧪
Tumour-wide RNA splicing aberrations generate actionable public neoantigens | Nature
T cell-based immunotherapies hold promise in treating cancer by leveraging the immune system’s recognition of cancer-specific antigens1. However, their efficacy is limited in tumours with few somatic mutations and substantial intratumoural heterogeneity2–4. Here we introduce a previously uncharacterized class of tumour-wide public neoantigens originating from RNA splicing aberrations in diverse cancer types. We identified T cell receptor clones capable of recognizing and targeting neoantigens derived from aberrant splicing in GNAS and RPL22. In cases with multi-site biopsies, we detected the tumour-wide expression of the GNAS neojunction in glioma, mesothelioma, prostate cancer and liver cancer. These neoantigens are endogenously generated and presented by tumour cells under physiologic conditions and are sufficient to trigger cancer cell eradication by neoantigen-specific CD8+ T cells. Moreover, our study highlights a role for dysregulated splicing factor expression in specific cancer
doi.org
March 20, 2025 at 3:10 AM
sailorrooscout.bsky.social
Each vaccine is designed using genetic material from the patient’s tumor- DNA mutations in the cancer cells that cause unique proteins to form on the cells’ surfaces. These proteins, called neoantigens, serve as the targets the vaccine trains immune cells called T-cells to attack.
June 29, 2026 at 4:10 PM
magarianblander.bsky.social
@drjonlim.bsky.social & @reisesousalab.bsky.social show cDC1s & DNGR1 favor "tethered" neoantigens from F-actin proteins, trapping them in necrotic debris for better cross-presentation! Calls for prioritizing these neoantigens for cancer vaccine design #Immunotherapy www.nature.com/articles/s41...
Cross-presentation of dead cell-associated antigens shapes the neoantigenic landscape of tumor immunity - Nature Immunology
Here the authors show DNGR-1 expressed by cDC1s promotes CD8⁺ T cell priming to cytoskeletal neoantigens from dying tumor cells, thereby shaping cancer immune visibility and tumor evolution through im...
www.nature.com
January 2, 2026 at 7:19 PM
sailorrooscout.bsky.social
Each vaccine is designed using genetic material from the patient’s tumor- DNA mutations in the cancer cells that cause unique proteins to form on the cells’ surfaces. These proteins, called neoantigens, serve as the targets the vaccine trains immune cells called T-cells to attack.
September 11, 2026 at 4:08 PM
atanas-g-atanasov.bsky.social
🚨 Big developments in cancer research!

🎯 Neoantigens are revolutionizing cancer vaccines, making treatments smarter & more personalized. Explore how this could transform healthcare 👇

🔗 inpst.net/the-landscap...

🌐 #CancerResearch #Innovation #INPST #CRBIOTECH
January 25, 2025 at 2:34 PM
doublewhammied.bsky.social
"Creating the vax starts w/neoantigens, bits of mutant protein pulld frm individual pts’ tumors aftr genetic sequencing ... 2 'school the immune system.' Neoantigens are an impt target not only 2 ward off recurrence but also avert damage in healthy cells." #CanSky
www.statnews.com/2025/02/05/p...
Personalized cancer vaccine shows potential in kidney cancer
In a Phase 1 study, nine people with advanced kidney cancer became cancer free after receiving personalized vaccines.
www.statnews.com
February 5, 2025 at 9:48 PM
bachynski.bsky.social
“Scientists sequence a patient's tumor to identify up to 34 unique molecular fingerprints called neoantigens and encode them into a custom vaccine. When it's injected, the vaccine trains T cells to recognize and target those specific neoantigens, giving the immune system a blueprint”
June 1, 2026 at 12:44 PM
daniellebeckman.bsky.social
Guess the anti-mRNA vaxx mob will also be against curing cancer.
www.nature.com/articles/s41...
RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer "Here we find that mRNA–lipoplex vaccines against somatic mutation-derived neoantigens may solve this challenge in pancreatic ductal adenocarcinoma (PDAC), a lethal cancer with few mutations"
February 21, 2025 at 10:21 PM
sailorrooscout.bsky.social
In the trial, each vaccine contained the information needed for the immune system to identify 34 of the top neoantigens that the researchers believed would be the best targets. Once their vaccine was ready -usually about four to six weeks after surgery- patients received up to nine doses spaced
June 29, 2026 at 4:11 PM
sailorrooscout.bsky.social
In the trial, each vaccine contained the information needed for the immune system to identify 34 of the top neoantigens that the researchers believed would be the best targets. Once their vaccine was ready -usually about four to six weeks after surgery- patients received up to nine doses spaced
September 11, 2026 at 4:08 PM
natchembio.nature.com
Small molecules can covalently modify proteins and generate covalent neoantigens, triggering immune responses. Now, a chemoproteomic platform enables the discovery of covalent neoantigens, which can also be harnessed for immunotherapeutic applications

www.nature.com/articles/s41...
Expanding the repertoire of chemically induced covalent neoantigens - Nature Chemical Biology
Small molecules can covalently modify proteins to generate hapten-modified peptides, triggering T cell-mediated immune responses. Now a chemoproteomic platform enables the discovery of covalent neoant...
www.nature.com
July 31, 2026 at 5:20 PM
erictopol.bsky.social
A vaccine to prevent colon cancer.
Proof-of-concept for strong immune response and safety via neoantigens given to people carrying mutations for Lynch syndrome
nature.com/articles/s41...
Nous-209 neoantigen vaccine for cancer prevention in Lynch syndrome carriers: a phase 1b/2 trial - Nature Medicine
In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficie...
nature.com
January 16, 2026 at 4:27 PM
sailorrooscout.bsky.social
The study has been published in Nature. YES, it is PEER-REVIEWED.
• www.nature.com/articles/s41...

IMPORTANT THINGS TO NOTE ‼️
IMPORTANT THINGS TO NOTE !! • KEEP IN MIND THESE ARE RESULTS THAT HAVE HELD UP APPROXIMATELY THREE YEARS showing that benefits demonstrated years ago have held up over time. That is ASTOUNDING. • Researchers say the results of a Phase I trial of an therapeutic cancer vaccine aimed at preventing kidney cancer show promise. • This new study found that ALL patients with ADVANCED stage kidney cancer had successful anti-cancer immune responses AND have remained CANCER-FREE approximately THREE years after treatment. • The study, demonstrates the potential of personalized vaccines to change the course of certain cancer types, but larger, longer trials are needed to confirm this approach. • Cancer vaccines developed with different molecular recipes are still in their early stages, before strong conclusions can be made. • While the findings are encouraging, the vaccine is still in early testing and will likely take years before it becomes widely available. How personalized peptide cancer vaccines work Scientists identify neoantigens, abnormal proteins produced by cancer cells. They take a sample of the patient's mutated cancer cells. The neoantigens are used to create a vaccine tailored to the patient's tumor. The vaccine is administered, prompting the immune system to target the cancer cells with those proteins. The immune system's T-cells attack and destroy the tumor cells, shrinking the cancer. ABSTRACT Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase l trial (ClinicalTrials.gov identifier NCTO2950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage Ill or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 months after surgery, none of the 9 participants enrolled in the study had a recurrence of RCC. No dose-limiting toxicities were observed. All patients generated T-cell immune responses against the PCV antigens, including to RCC driver mutations in VHL, PBRM1, BAP1, KDM5C and PIK. Following vaccination, there was a durable expansion of peripheral T-cell clones. Moreover, T-cell reactivity against autologous tumours was detected in seven out of nine patients. Our results demonstrate that neoantigen-targeting PCVs in high-risk RCC are highly immunogenic, capable of targeting key driver mutations and can induce antitumour immunity. These observations, in conjunction with the absence of recurrence in all nine vaccinated patients, highlights the promise of PCVs as effective adjuvant therapy in RCC. This study involved a large and collaborative team across multiple institutions, with key leadership from co-senior authors Toni Choueiri, Derin Keskin, Patrick Ott, and Catherine Wu from DFCI. Research reported in this release was supported by the National Institutes of Health under award numbers 1R37CA279822-01 and P30CA016359. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The research was also funded by the Gateway for Cancer Research, U.S. Department of Defense, Louis Goodman and Alfred Gilman Yale Scholar Fund, Yale Cancer Center, Dana-Farber/ Harvard Cancer Center, Harvard Medical School, Trust Family Foundation, Michael Brigham, Pan Mass Challenge, Hinda L. and Arthur Marcus Foundation, The Loker Pinard Fund for Kidney Cancer Research at Dana-Farber Cancer Institute, and Conquer Cancer Foundation/Sontag Foundation.
February 26, 2025 at 5:02 PM
cp-cell.bsky.social
Now online! Mis-splicing-derived neoantigens and cognate TCRs in splicing factor mutant leukemias
Mis-splicing-derived neoantigens and cognate TCRs in splicing factor mutant leukemias
Common oncogenic RNA splicing factor mutations in myeloid malignancies generate recurrent splicing-derived neoantigens, which can be selectively targeted using a T cell receptor-based approach.
dlvr.it
April 24, 2025 at 12:41 PM
patrickhwumd.bsky.social
#ScienceSaturday 🧵

➡️ Immunotherapies targeting neoantigens can be effective in mediating long-term durable responses in advanced cancer patients. However, identifying these neoantigens from metastatic tumors can be logistically challenging.
February 1, 2025 at 9:31 PM
labwaggoner.bsky.social
Preprint: Targeting Neoantigens Conserved Across Organs and Species Overcomes Tumor Immune Escape @bhardwajlab.bsky.social @sinaiimmuno.bsky.social
papers.ssrn.com/sol3/papers....
February 8, 2026 at 6:28 PM
drjanicekirsch.bsky.social
True on all counts.
But the rapid identification of neoantigens and the versatility of mRNA platforms will increase their creation.
Production can be a bottleneck but one that can be overcome.
August 21, 2026 at 10:40 PM
elizsmckenna.bsky.social
Now online in Cancer Discovery @aacrjournals.bsky.social: Recurrent Immunogenic Neoantigens and Their Cognate T-cell Receptors in Treatment-Resistant Metastatic Prostate Cancer - by Nofar Gumpert, Shira Sagie, @yardenasamuels.bsky.social, and colleagues doi.org/10.1158/2159...
October 13, 2025 at 11:00 AM
peiferlabunc.bsky.social
Neoantigen vaccine-specific T cells were induced in all 14 patients and were mostly high-magnitude and durable, although the responses were weaker in three of the patients 5/n
Magnitude of T cell responses to individual neoantigens detected by ex vivo IFNγ ELISpot for all participants.
May 13, 2026 at 11:26 AM
oawlab.bsky.social
Excited to announce a new paper out today in @cp-cell.bsky.social discovering RNA mis-splicing derived neoantigens & their cognate T cell receptors (TCRs) as well as characterization of endogenous neoantigen T cells in leukemia patients.

authors.elsevier.com/sd/article/S...
ScienceDirect.com | Science, health and medical journals, full text articles and books.
authors.elsevier.com
April 23, 2025 at 8:30 PM