Local Immunotherapy of Cancer: Innovative Approaches to Harnessing Tumor-Specific Immune Responses

Vivek Murthy, Janna Minehart, Daniel H. Sterman

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses. Our current approach to reversing this process for antitumor effect involves mainly systemic administration of immunotherapeutic agents, many of which have become standard of care in the management of a variety of cancers. Despite this, we are still learning how best to administer these drugs alone and in combination to maximize efficacy while minimizing adverse events. Increasing evidence suggests that comparable efficacy may be achieved by local administration of immunotherapies in the tumor or tumor-draining lymph nodes with substantially lower doses and better tolerability, even with combination therapy. Herein, we review the literature on intratumoral and intranodal immunotherapies in preclinical models and early-phase studies, with particular emphasis on approaches potentially suitable for translation to larger-scale clinical trials.

Original languageEnglish (US)
JournalJournal of the National Cancer Institute
Volume109
Issue number12
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

Fingerprint

Immunotherapy
Neoplasms
Lymph Nodes
Immunologic Monitoring
Antigen Presentation
Regulatory T-Lymphocytes
Standard of Care
Immunosuppressive Agents
Blood Vessels
Down-Regulation
Clinical Trials
Learning
Lymphocytes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Local Immunotherapy of Cancer : Innovative Approaches to Harnessing Tumor-Specific Immune Responses. / Murthy, Vivek; Minehart, Janna; Sterman, Daniel H.

In: Journal of the National Cancer Institute, Vol. 109, No. 12, 01.12.2017.

Research output: Contribution to journalReview article

@article{0f6ef5c98d314204ac5745150e8072d5,
title = "Local Immunotherapy of Cancer: Innovative Approaches to Harnessing Tumor-Specific Immune Responses",
abstract = "Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses. Our current approach to reversing this process for antitumor effect involves mainly systemic administration of immunotherapeutic agents, many of which have become standard of care in the management of a variety of cancers. Despite this, we are still learning how best to administer these drugs alone and in combination to maximize efficacy while minimizing adverse events. Increasing evidence suggests that comparable efficacy may be achieved by local administration of immunotherapies in the tumor or tumor-draining lymph nodes with substantially lower doses and better tolerability, even with combination therapy. Herein, we review the literature on intratumoral and intranodal immunotherapies in preclinical models and early-phase studies, with particular emphasis on approaches potentially suitable for translation to larger-scale clinical trials.",
author = "Vivek Murthy and Janna Minehart and Sterman, {Daniel H.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1093/jnci/djx097",
language = "English (US)",
volume = "109",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "12",

}

TY - JOUR

T1 - Local Immunotherapy of Cancer

T2 - Innovative Approaches to Harnessing Tumor-Specific Immune Responses

AU - Murthy, Vivek

AU - Minehart, Janna

AU - Sterman, Daniel H.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses. Our current approach to reversing this process for antitumor effect involves mainly systemic administration of immunotherapeutic agents, many of which have become standard of care in the management of a variety of cancers. Despite this, we are still learning how best to administer these drugs alone and in combination to maximize efficacy while minimizing adverse events. Increasing evidence suggests that comparable efficacy may be achieved by local administration of immunotherapies in the tumor or tumor-draining lymph nodes with substantially lower doses and better tolerability, even with combination therapy. Herein, we review the literature on intratumoral and intranodal immunotherapies in preclinical models and early-phase studies, with particular emphasis on approaches potentially suitable for translation to larger-scale clinical trials.

AB - Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses. Our current approach to reversing this process for antitumor effect involves mainly systemic administration of immunotherapeutic agents, many of which have become standard of care in the management of a variety of cancers. Despite this, we are still learning how best to administer these drugs alone and in combination to maximize efficacy while minimizing adverse events. Increasing evidence suggests that comparable efficacy may be achieved by local administration of immunotherapies in the tumor or tumor-draining lymph nodes with substantially lower doses and better tolerability, even with combination therapy. Herein, we review the literature on intratumoral and intranodal immunotherapies in preclinical models and early-phase studies, with particular emphasis on approaches potentially suitable for translation to larger-scale clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=85041851622&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041851622&partnerID=8YFLogxK

U2 - 10.1093/jnci/djx097

DO - 10.1093/jnci/djx097

M3 - Review article

C2 - 29546344

AN - SCOPUS:85041851622

VL - 109

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 12

ER -