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Comment
. 2021 Apr 20;2(4):100244.
doi: 10.1016/j.xcrm.2021.100244.

Hypoxia-inducible CAR expression: An answer to the on-target/off-tumor dilemma?

Brooke Prinzing  1 , Giedre Krenciute  1
Affiliations
Comment

Hypoxia-inducible CAR expression: An answer to the on-target/off-tumor dilemma?

Brooke Prinzing et al. Cell Rep Med. .

Abstract

On-target/off-tumor toxicity is one of the major concerns regarding CAR T-cell therapy. Kosti et al.1 demonstrate that this form of toxicity can be prevented by designing a CAR whose expression is controlled by oxygen levels in the tumor environment.

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Figures

Figure 1
Figure 1
HypoxiCAR expression is tightly controlled by the amount of oxygen in the environment Top: under hypoxic conditions, HIF1α binds to hypoxia response elements (HREs) within the promoter, increasing CAR transcription. Bottom: under normoxic conditions, the oxygen-dependent degradation domain (ODD) attached to the C terminus of the CAR is ubiquitinated, directing the CAR to the proteasome for degradation.
See this image and copyright information in PMC

Comment on

  • Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors.
    Kosti P, Opzoomer JW, Larios-Martinez KI, Henley-Smith R, Scudamore CL, Okesola M, Taher MYM, Davies DM, Muliaditan T, Larcombe-Young D, Woodman N, Gillett CE, Thavaraj S, Maher J, Arnold JN. Kosti P, et al. Cell Rep Med. 2021 Apr 9;2(4):100227. doi: 10.1016/j.xcrm.2021.100227. eCollection 2021 Apr 20. Cell Rep Med. 2021. PMID: 33948568 Free PMC article.

References

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