At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy Journal Article
| Authors: | Callahan, M. K.; Wolchok, J. D. |
| Article Title: | At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy |
| Abstract: | It is increasingly appreciated that cancers are recognized by the immune system, and under some circumstances, the immune system may control or even eliminate tumors. The modulation of signaling via coinhibitory or costimulatory receptors expressed on T cells has proven to be a potent way to amplify antitumor immune responses. This approach has been exploited successfully for the generation of a new class of anticancer therapies, "checkpoint-blocking" antibodies, exemplified by the recently FDA-approved agent, ipilimumab, an antibody that blocks the coinhibitory receptor CTLA-4. Capitalizing on the success of ipilimumab, agents that target a second coinhibitory receptor, PD-1, or its ligand, PD-L1, are in clinical development. Lessons learned from treating patients with CTLA-4 and PD-1 pathway-blocking antibodies will be reviewed, with a focus on concepts likely to inform the clinical development and application of agents in earlier stages of development. See related review At the bench: Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. © Society for Leukocyte Biology. |
| Keywords: | cancer survival; protein expression; unclassified drug; overall survival; hepatitis; placebo; cancer combination chemotherapy; cancer growth; diarrhea; dose response; drug dose comparison; drug efficacy; drug withdrawal; nonhuman; side effect; solid tumor; drug approval; pancreas cancer; temozolomide; colorectal cancer; t lymphocyte; cytotoxic t lymphocyte antigen 4 antibody; dacarbazine; glycoprotein gp 100; ipilimumab; ticilimumab; unindexed drug; cancer immunotherapy; melanoma; ovary cancer; breast cancer; tumor volume; lung non small cell cancer; neuropathy; tumor antigen; kidney carcinoma; arthralgia; drug dose escalation; pneumonia; prostate cancer; pruritus; rash; hematologic malignancy; pancreatitis; melanoma b16; single drug dose; toxicity testing; adoptive transfer; stomach cancer; colitis; immunomodulation; dermatitis; inoperable cancer; drug half life; hypothyroidism; liver enzyme; peptide vaccine; tumor; corticosteroid; granulocyte macrophage colony stimulating factor vaccine; mycophenolic acid 2 morpholinoethyl ester; androgen deprivation therapy; cytopenia; antibody; chemoradiotherapy; immunosuppressive agent; uveitis; programmed death 1 ligand 1; programmed death 1 receptor; myopathy; metastatic melanoma; adrenal insufficiency; randomized controlled trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); phase 1 clinical trial (topic); hypophysitis; vitiligo; endpoints; conjunctivitis; pharmacological biomarker; thyroiditis; programmed death 1 ligand 1 antibody; programmed death 1 receptor antibody; tumor escape; nephritis; tumor necrosis factor antibody; sipuleucel t; hypophysis disease; nivolumab; amp 224; bms 936559; mk 3475; mpdl 3280a; pidilizumab; rg 7446; medi 4736 |
| Journal Title: | Journal of Leukocyte Biology |
| Volume: | 94 |
| Issue: | 1 |
| ISSN: | 0741-5400 |
| Publisher: | Federation of American Societies for Experimental Biology |
| Date Published: | 2013-07-01 |
| Start Page: | 41 |
| End Page: | 53 |
| Language: | English |
| DOI: | 10.1189/jlb.1212631 |
| PROVIDER: | scopus |
| PUBMED: | 23667165 |
| PMCID: | PMC4051187 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):1 - "Export Date: 1 August 2013" - "CODEN: JLBIE" - "Source: Scopus" |
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