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TNF-α inhibitor reduces drug-resistance to anti-PD-1: A mathematical model

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  • Xiulan Lai
  • Wenrui Hao
  • Avner Friedman

Abstract

Drug resistance is a primary obstacle in cancer treatment. In many patients who at first respond well to treatment, relapse occurs later on. Various mechanisms have been explored to explain drug resistance in specific cancers and for specific drugs. In this paper, we consider resistance to anti-PD-1, a drug that enhances the activity of anti-cancer T cells. Based on results in experimental melanoma, it is shown, by a mathematical model, that resistances to anti-PD-1 can be significantly reduced by combining it with anti-TNF-α. The model is used to simulate the efficacy of the combined therapy with different range of doses, different initial tumor volume, and different schedules. In particular, it is shown that under a course of treatment with 3-week cycles where each drug is injected in the first day of either week 1 or week 2, injecting anti-TNF-α one week after anti-PD-1 is the most effective schedule in reducing tumor volume.

Suggested Citation

  • Xiulan Lai & Wenrui Hao & Avner Friedman, 2020. "TNF-α inhibitor reduces drug-resistance to anti-PD-1: A mathematical model," PLOS ONE, Public Library of Science, vol. 15(4), pages 1-21, April.
    • Handle: RePEc:plo:pone00:0231499
    DOI: 10.1371/journal.pone.0231499
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    1. Moshe Sade-Feldman & Yunxin J. Jiao & Jonathan H. Chen & Michael S. Rooney & Michal Barzily-Rokni & Jean-Pierre Eliane & Stacey L. Bjorgaard & Marc R. Hammond & Hans Vitzthum & Shauna M. Blackmon & De, 2017. "Resistance to checkpoint blockade therapy through inactivation of antigen presentation," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
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