TY - JOUR
T1 - Intratumoral immunotherapy for early-stage solid tumors
AU - Hong, Wan Xing
AU - Haebe, Sarah
AU - Lee, Andrew S.
AU - Benedikt Westphalen, C.
AU - Norton, Jeffrey A.
AU - Jiang, Wen
AU - Levy, Ronald
N1 - Funding Information:
This work was supported by grants from the National Institute of Health (5R35CA197353; to R. Levy), Cancer Prevention and Research Institute of Texas (RR180017), The National Cancer Institute (K08CA241070), and the Susan G. Komen Foundation (CCR19605871; to W. Jiang). W.X. Hong is supported by The National Institute of Health (5T32AI07290). S. Haebe is supported by The German Cancer Aid (Mildred-Scheel postdoctoral fellowship).
Funding Information:
R. Levy is a paid consultant for Five Prime, Quadriga, GigaGen, Teneobio, Sutro, Checkmate, Nurix, Dragonfly, Abpro, Apexigen, Viracta, Forty Seven, Spotlight, XCella, Immunocore, and Walking Fish, reports receiving commercial research grants from Bristol-Myers Squib and Janssen, and is an unpaid consultant/advisory board member for the Leukemia and Lymphoma Society and the Margaret Early Trust. No potential conflicts of interest were disclosed by the other authors.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/7
Y1 - 2020/7
N2 - The unprecedented benefits of immunotherapy in advanced malignancies have resulted in increased interests in exploiting immune stimulatory agents in earlier-stage solid tumors in the neoadjuvant setting. However, systemic delivery of immunotherapies may cause severe immune-related side-effects and hamper the development of combination treatments. Intratumoral delivery of neoadjuvant immunotherapy provides a promising strategy in harnessing the power of immunotherapy while minimizing off-target toxicities. The direct injection of immune stimulating agents into the tumor primes the local tumor-specific immunity to generate a systemic, durable clinical response. Intratumoral immunotherapy is a highly active area of investigation resulting in a plethora of agents, for example, immune receptor agonists, non-oncolytic and oncolytic viral therapies, being tested in preclinical and clinical settings. Currently, more than 20 neoadjuvant clinical trials exploring distinct intratumoral immune stimulatory agents and their combinations are ongoing. Practical considerations, including appropriate timing and optimal local delivery of immune stimulatory agents play an important role in safety and efficacy of this approach. Here, we discuss promising approaches in drug delivery technologies and opportunity for combining intratumoral immunotherapy with other cancer treatments and summarize the recent preclinical and clinical evidences that highlighted its promise as a part of routine oncologic care.
AB - The unprecedented benefits of immunotherapy in advanced malignancies have resulted in increased interests in exploiting immune stimulatory agents in earlier-stage solid tumors in the neoadjuvant setting. However, systemic delivery of immunotherapies may cause severe immune-related side-effects and hamper the development of combination treatments. Intratumoral delivery of neoadjuvant immunotherapy provides a promising strategy in harnessing the power of immunotherapy while minimizing off-target toxicities. The direct injection of immune stimulating agents into the tumor primes the local tumor-specific immunity to generate a systemic, durable clinical response. Intratumoral immunotherapy is a highly active area of investigation resulting in a plethora of agents, for example, immune receptor agonists, non-oncolytic and oncolytic viral therapies, being tested in preclinical and clinical settings. Currently, more than 20 neoadjuvant clinical trials exploring distinct intratumoral immune stimulatory agents and their combinations are ongoing. Practical considerations, including appropriate timing and optimal local delivery of immune stimulatory agents play an important role in safety and efficacy of this approach. Here, we discuss promising approaches in drug delivery technologies and opportunity for combining intratumoral immunotherapy with other cancer treatments and summarize the recent preclinical and clinical evidences that highlighted its promise as a part of routine oncologic care.
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U2 - 10.1158/1078-0432.CCR-19-3642
DO - 10.1158/1078-0432.CCR-19-3642
M3 - Review article
C2 - 32071116
AN - SCOPUS:85086643764
SN - 1078-0432
VL - 26
SP - 3091
EP - 3099
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -