A vaccine targeting mutant IDH1 in newly diagnosed glioma

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SUMMARY

The discussion centers on a novel vaccine targeting the IDH1(R132H) mutation in newly diagnosed gliomas, specifically in patients with World Health Organization grade 3 and 4 astrocytomas. The IDH1-vac vaccine has shown efficacy in inducing therapeutic T helper cell responses against IDH1(R132H)+ tumors in preclinical models. A phase I trial (NOA16, ClinicalTrials.gov identifier NCT02454634) involving 33 patients has been conducted to evaluate the vaccine's safety and immunogenicity. This represents a significant advancement in cancer immunotherapy, particularly for glioma treatment.

PREREQUISITES
  • Understanding of isocitrate dehydrogenase (IDH1) mutations in gliomas
  • Familiarity with major histocompatibility complex (MHC) class II presentation
  • Knowledge of cancer immunotherapy principles
  • Awareness of clinical trial phases and design
NEXT STEPS
  • Research the mechanisms of action for IDH1-vac vaccine
  • Explore the implications of the NOA16 trial results on glioma treatment
  • Investigate other cancer vaccines currently in clinical trials
  • Learn about the role of checkpoint inhibitors and CAR-T therapy in cancer immunotherapy
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Oncologists, cancer researchers, immunotherapy specialists, and medical professionals interested in the latest advancements in glioma treatment and cancer vaccine development.

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Mutated isocitrate dehydrogenase 1 (IDH1) defines a molecularly distinct subtype of diffuse glioma1,2,3. The most common IDH1 mutation in gliomas affects codon 132 and encodes IDH1(R132H), which harbours a shared clonal neoepitope that is presented on major histocompatibility complex (MHC) class II4,5. An IDH1(R132H)-specific peptide vaccine (IDH1-vac) induces specific therapeutic T helper cell responses that are effective against IDH1(R132H)+ tumours in syngeneic MHC-humanized mice4,6,7,8. Here we describe a multicentre, single-arm, open-label, first-in-humans phase I trial that we carried out in 33 patients with newly diagnosed World Health Organization grade 3 and 4 IDH1(R132H)+ astrocytomas (Neurooncology Working Group of the German Cancer Society trial 16 (NOA16), ClinicalTrials.gov identifier NCT02454634).

Are cancer vaccines a super new thing? I have not heard of a vaccine for cancer before.
https://www.nature.com/articles/s41586-021-03363-z
 
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Greg Bernhardt said:
Are cancer vaccines a super new thing? I have not heard of a vaccine for cancer before.
https://www.nature.com/articles/s41586-021-03363-z

The idea of creating a vaccine to prime the immune system to attack cancer is fairly new, though many groups are working on this idea. For example, here's a PF thread from 3 years ago discussing research related to anti-cancer vaccines: https://www.physicsforums.com/threads/new-cancer-research-at-stanford.938605/

Here's a more general article on the topic: https://www.cancerresearch.org/immunotherapy/treatment-types/cancer-vaccines

The idea of anti-cancer vaccines is related to the broader idea of cancer immunotherapy, which is one of the big new ideas in cancer research. Basically, the goal of cancer immunotherapy is to use the body's own immune system to fight cancer. Current cancer immunotherapy drugs being used in the clinic include checkpoint inhibitor therapy (which helps get around defenses that cancer cells use to hide from the immune system; this idea was awarded the Nobel Prize in Medicine in 2018) and CAR-T therapy (which involves engineering immune cells to better be able to fight cancer cells).
 
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