Cancer immunotherapy beyond immune checkpoint inhibitors

Julian A. Marin-Acevedo, Aixa E. Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou

Research output: Contribution to journalReview article

31 Citations (Scopus)

Abstract

Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy, however, extends beyond immune checkpoint therapy by using new molecules such as chimeric monoclonal antibodies and antibody drug conjugates that target malignant cells and promote their destruction. Genetically modified T cells expressing chimeric antigen receptors are able to recognize specific antigens on cancer cells and subsequently activate the immune system. Native or genetically modified viruses with oncolytic activity are of great interest as, besides destroying malignant cells, they can increase anti-tumor activity in response to the release of new antigens and danger signals as a result of infection and tumor cell lysis. Vaccines are also being explored, either in the form of autologous or allogenic tumor peptide antigens, genetically modified dendritic cells that express tumor peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of specific tumor markers. Most of these agents are yet under development, but they promise to be important options to boost the host immune system to control and eliminate malignancy. In this review, we have provided detailed discussion of different forms of immunotherapy agents other than checkpoint-modifying drugs. The specific focus of this manuscript is to include first-in-human phase I and phase I/II clinical trials intended to allow the identification of those drugs that most likely will continue to develop and possibly join the immunotherapeutic arsenal in a near future.

Original languageEnglish (US)
Article number8
JournalJournal of Hematology and Oncology
Volume11
Issue number1
DOIs
StatePublished - Jan 12 2018

Fingerprint

Immunotherapy
Immune System
Neoplasms
CD274 Antigen
Programmed Cell Death 1 Receptor
Oncolytic Viruses
Pharmaceutical Preparations
Antigens
Phase II Clinical Trials
Peptides
Clinical Trials, Phase I
Antigen Receptors
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Tumor Biomarkers
Dendritic Cells
Vaccines
Monoclonal Antibodies
RNA
Viruses

Keywords

  • Antibody drug conjugates
  • Chimeric antigen receptor therapy
  • Immunotherapy
  • Oncolytic viruses
  • Tumor vaccines
  • Tumor-directed monoclonal antibodies
  • Viral gene therapy

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

Cite this

Cancer immunotherapy beyond immune checkpoint inhibitors. / Marin-Acevedo, Julian A.; Soyano, Aixa E.; Dholaria, Bhagirathbhai; Knutson, Keith L; Lou, Yanyan.

In: Journal of Hematology and Oncology, Vol. 11, No. 1, 8, 12.01.2018.

Research output: Contribution to journalReview article

Marin-Acevedo, Julian A. ; Soyano, Aixa E. ; Dholaria, Bhagirathbhai ; Knutson, Keith L ; Lou, Yanyan. / Cancer immunotherapy beyond immune checkpoint inhibitors. In: Journal of Hematology and Oncology. 2018 ; Vol. 11, No. 1.
@article{43bc38614af343a7b6650e997cb9a092,
title = "Cancer immunotherapy beyond immune checkpoint inhibitors",
abstract = "Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy, however, extends beyond immune checkpoint therapy by using new molecules such as chimeric monoclonal antibodies and antibody drug conjugates that target malignant cells and promote their destruction. Genetically modified T cells expressing chimeric antigen receptors are able to recognize specific antigens on cancer cells and subsequently activate the immune system. Native or genetically modified viruses with oncolytic activity are of great interest as, besides destroying malignant cells, they can increase anti-tumor activity in response to the release of new antigens and danger signals as a result of infection and tumor cell lysis. Vaccines are also being explored, either in the form of autologous or allogenic tumor peptide antigens, genetically modified dendritic cells that express tumor peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of specific tumor markers. Most of these agents are yet under development, but they promise to be important options to boost the host immune system to control and eliminate malignancy. In this review, we have provided detailed discussion of different forms of immunotherapy agents other than checkpoint-modifying drugs. The specific focus of this manuscript is to include first-in-human phase I and phase I/II clinical trials intended to allow the identification of those drugs that most likely will continue to develop and possibly join the immunotherapeutic arsenal in a near future.",
keywords = "Antibody drug conjugates, Chimeric antigen receptor therapy, Immunotherapy, Oncolytic viruses, Tumor vaccines, Tumor-directed monoclonal antibodies, Viral gene therapy",
author = "Marin-Acevedo, {Julian A.} and Soyano, {Aixa E.} and Bhagirathbhai Dholaria and Knutson, {Keith L} and Yanyan Lou",
year = "2018",
month = "1",
day = "12",
doi = "10.1186/s13045-017-0552-6",
language = "English (US)",
volume = "11",
journal = "Journal of Hematology and Oncology",
issn = "1756-8722",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Cancer immunotherapy beyond immune checkpoint inhibitors

AU - Marin-Acevedo, Julian A.

AU - Soyano, Aixa E.

AU - Dholaria, Bhagirathbhai

AU - Knutson, Keith L

AU - Lou, Yanyan

PY - 2018/1/12

Y1 - 2018/1/12

N2 - Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy, however, extends beyond immune checkpoint therapy by using new molecules such as chimeric monoclonal antibodies and antibody drug conjugates that target malignant cells and promote their destruction. Genetically modified T cells expressing chimeric antigen receptors are able to recognize specific antigens on cancer cells and subsequently activate the immune system. Native or genetically modified viruses with oncolytic activity are of great interest as, besides destroying malignant cells, they can increase anti-tumor activity in response to the release of new antigens and danger signals as a result of infection and tumor cell lysis. Vaccines are also being explored, either in the form of autologous or allogenic tumor peptide antigens, genetically modified dendritic cells that express tumor peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of specific tumor markers. Most of these agents are yet under development, but they promise to be important options to boost the host immune system to control and eliminate malignancy. In this review, we have provided detailed discussion of different forms of immunotherapy agents other than checkpoint-modifying drugs. The specific focus of this manuscript is to include first-in-human phase I and phase I/II clinical trials intended to allow the identification of those drugs that most likely will continue to develop and possibly join the immunotherapeutic arsenal in a near future.

AB - Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy, however, extends beyond immune checkpoint therapy by using new molecules such as chimeric monoclonal antibodies and antibody drug conjugates that target malignant cells and promote their destruction. Genetically modified T cells expressing chimeric antigen receptors are able to recognize specific antigens on cancer cells and subsequently activate the immune system. Native or genetically modified viruses with oncolytic activity are of great interest as, besides destroying malignant cells, they can increase anti-tumor activity in response to the release of new antigens and danger signals as a result of infection and tumor cell lysis. Vaccines are also being explored, either in the form of autologous or allogenic tumor peptide antigens, genetically modified dendritic cells that express tumor peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of specific tumor markers. Most of these agents are yet under development, but they promise to be important options to boost the host immune system to control and eliminate malignancy. In this review, we have provided detailed discussion of different forms of immunotherapy agents other than checkpoint-modifying drugs. The specific focus of this manuscript is to include first-in-human phase I and phase I/II clinical trials intended to allow the identification of those drugs that most likely will continue to develop and possibly join the immunotherapeutic arsenal in a near future.

KW - Antibody drug conjugates

KW - Chimeric antigen receptor therapy

KW - Immunotherapy

KW - Oncolytic viruses

KW - Tumor vaccines

KW - Tumor-directed monoclonal antibodies

KW - Viral gene therapy

UR - http://www.scopus.com/inward/record.url?scp=85040457867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040457867&partnerID=8YFLogxK

U2 - 10.1186/s13045-017-0552-6

DO - 10.1186/s13045-017-0552-6

M3 - Review article

VL - 11

JO - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

SN - 1756-8722

IS - 1

M1 - 8

ER -