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Editorial
. 2019 Jan 1;10(1):1-2.
doi: 10.18632/oncotarget.26509.

TIL therapy and anti-CTLA4: can they co-exist?

Marie-Andrée Forget  1   2 , Cara Haymaker  1   2 , Rodabe N Amaria  1   2 , Chantale Bernatchez  1   2
Affiliations
Editorial

TIL therapy and anti-CTLA4: can they co-exist?

Marie-Andrée Forget et al. Oncotarget. .
No abstract available

Keywords: CTLA4; TIL; metastatic melanoma.

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Figures

Figure 1
Figure 1. Proposed model for a potential impact of anti-CTLA4 exposure on IL-2 expanded TIL during initial activation in the REP
Panel A. depicts the expected proliferative outcome after checkpoint naïve IL-2 propagated TIL are activated at the initial step of the REP. TIL are activated through their TCR following interaction with anti-CD3 (OKT3) loaded on the surface of the feeder cells (pool of 3 to 6 normal donors irradiated PBMC). The feeder cells represent an important expansion platform in the initial activation of the TIL, providing TCR stimulation as well as costimulation through expression of CD80/CD86, ligands of the CD28 molecule expressed at the surface of the TIL. Panel B. shows the theoretical outcome of a anti-CTLA4 exposed TIL in the initial step of activation of the REP. Unlike the checkpoint naïve TIL, the anti-CTLA4 exposed TIL contain a high level of intracellular CTLA molecules which quickly accumulate at the surface of the TIL at the time of TCR activation through anti-CD3 interaction. Following surface accumulation, the CTLA4 molecules compete against the outnumbered CD28 molecules for binding of the CD80/CD86 molecules. This binding results in suppression of the TIL activation and proliferation, leading to a suboptimal TIL expansion through the REP. Panel C. illustrates the protection from suppression provided by the addition of anti-CTLA4 to the REP. Blocking CTLA4 access to CD80/CD86 gives the opportunity for CD28 to interact with the ligands for positive feedback.
See this image and copyright information in PMC

References

    1. Rosenberg SA, et al. Clin Cancer Res. 2011;17:4550–57. doi: 10.1158/1078-0432.CCR-11-0116. - DOI - PMC - PubMed
    1. Radvanyi LG, et al. Clin Cancer Res. 2012;18:6758–70. doi: 10.1158/1078-0432.CCR-12-1177. - DOI - PMC - PubMed
    1. Pilon-Thomas S, et al. J Immunother. 2012;35:615–20. doi: 10.1097/CJI.0b013e31826e8f5f. - DOI - PMC - PubMed
    1. Besser MJ, et al. Clin Cancer Res. 2013;19:4792–800. doi: 10.1158/1078-0432.CCR-13-0380. - DOI - PubMed
    1. Andersen R, et al. Clin Cancer Res. 2016;22:3734–45. doi: 10.1158/1078-0432.CCR-15-1879. - DOI - PubMed

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