TY - JOUR

T1 - Tumor-infiltrating lymphocytes for adoptive cell therapy

T2 - recent advances, challenges, and future directions

AU - Granhøj, Joachim Stoltenborg

AU - Witness Præst Jensen, Agnete

AU - Presti, Mario

AU - Met, Özcan

AU - Svane, Inge Marie

AU - Donia, Marco

N1 - Publisher Copyright: © 2022 Informa UK Limited, trading as Taylor & Francis Group.

PY - 2022

Y1 - 2022

N2 - Introduction: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a highly personalized type of cancer immunotherapy. TIL-based ACT exploits naturally occurring TILs, derived from the patients’ tumor. This treatment has shown consistent clinical responses in melanoma, and recent results point toward a potential use in multiple cancer diagnoses. However, several limitations have restricted the clinical development and adaptation of TIL-based ACT. Areas covered: In this review, we present the principles of TIL-based ACT and discuss the most significant limitations for therapeutic efficacy and its widespread application. The topics of therapeutic resistance (both innate and acquired), treatment-related toxicity, and the novel research topic of metabolic barriers in the tumor microenvironment (TME) are covered. Expert opinion: There are many ongoing areas of research focusing on improving clinical efficacy and optimizing TIL-based ACT. Many strategies have shown a great potential, particularly strategies advancing TIL efficacy (such as increasing and harnessing ex vivo the sub-population of tumor-reactive TILs) and manufacturing processes. Novel approaches can help overcome current limitations and potentially result in TIL-based ACT entering the mainstream of cancer therapy across tumor types.

AB - Introduction: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a highly personalized type of cancer immunotherapy. TIL-based ACT exploits naturally occurring TILs, derived from the patients’ tumor. This treatment has shown consistent clinical responses in melanoma, and recent results point toward a potential use in multiple cancer diagnoses. However, several limitations have restricted the clinical development and adaptation of TIL-based ACT. Areas covered: In this review, we present the principles of TIL-based ACT and discuss the most significant limitations for therapeutic efficacy and its widespread application. The topics of therapeutic resistance (both innate and acquired), treatment-related toxicity, and the novel research topic of metabolic barriers in the tumor microenvironment (TME) are covered. Expert opinion: There are many ongoing areas of research focusing on improving clinical efficacy and optimizing TIL-based ACT. Many strategies have shown a great potential, particularly strategies advancing TIL efficacy (such as increasing and harnessing ex vivo the sub-population of tumor-reactive TILs) and manufacturing processes. Novel approaches can help overcome current limitations and potentially result in TIL-based ACT entering the mainstream of cancer therapy across tumor types.

KW - Adoptive cell therapy

KW - cell therapy

KW - cellular immunotherapy

KW - resistance to immunotherapy

KW - TILs

KW - tumor-infiltrating lymphocytes

U2 - 10.1080/14712598.2022.2064711

DO - 10.1080/14712598.2022.2064711

M3 - Review

C2 - 35414331

AN - SCOPUS:85128843597

VL - 22

SP - 627

EP - 641

JO - Expert Opinion on Biological Therapy

JF - Expert Opinion on Biological Therapy

SN - 1471-2598

IS - 5

ER -