C-MYB overexpression for exhaustion resistant car-t cell therapies

Active Project Grant Awarded Last action

Award ID
R43CA295178
Recipient
Awarding agency
Obligated
$400,000

Award facts

Assistance listing
93.395 Cancer Treatment Research
Completion date 62% complete
Originally
Place of performance
Minnesota, USA

Award details come from USAspending.gov.

Description

Abstract
Chimeric antigen receptor or car-t cells are curative in various hematologic malignancies, with six products obtaining FDA approval since 2017. However, the same mechanisms that enable high therapeutic efficacy in some patients can lead to overstimulation and functional exhaustion of the car-t cell therapy, resulting in PAR- tial remission and/or disease relapse. Technologies that limit car-t cell exhaustion are likely to improve thera- peutic outcomes by promoting anti-tumor functionality and enhancing the duration of therapeutic activity. In mice, t cells engineered to overexpress specific transcription factors have enhanced anti-tumor activity by LIM- iting exhaustion. However, when considering car-t cells for human therapeutics, fine-tuning the expression of factors that regulate transcriptional reprogramming events to curtail exhaustion while maintaining anti-tumor functionality is not easily addressed with current methods of cellular programming. This proposal is focused on overexpressing the transcription factor c-MYB as part of the response of this grant to nosi not-NS-22-017 in car-t cell therapy for enhanced therapeutic efficacy. Critical to our ability to DE- velop optimal car-t cells with this approach, we use proprietary precision gene editing technology, GE- neweld. Geneweld permits the precise, reproducible integration of multi-kilobase cargo DNA into loci with base-pair precision, thus permitting improved expression of multiple cassettes for the development and ad- vancement of human cell therapy manufacturing. This phase i proposal is focused on demonstrating the feasi- bility of producing c-MYB-enforced car-t cells that provide sustained anti-tumor activity, ultimately resulting in clinical improvements over the current FDA-approved car-t cell therapies.

Transactions

Action Obligated Date
Amendment $0
Original award $400,000

Quick answers

Who received award R43CA295178?

R43CA295178 was awarded to Lifengine Animal Health Laboratories Incorporated by National Cancer Institute (National Institutes of Health) on August 4, 2025.

How much is award R43CA295178 worth?

$400,000 has been obligated on R43CA295178.

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