cancer immunotherapy
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Introduction
The 4 FDA-approved cancer immunotherapies are checkpoint inhibitors
Epidemiology
- men tend to do better than women with cancer immunotherapy[5]
Adverse effects
- checkpoint inhibitors may allow the immune system to attack intestines, liver, lungs, kidneys, adrenal, pituitary, heart, & the pancreas
- severe immune reactions in nearly 20% of patients, 50% if combination therapy used
Laboratory
- ploidy measurement or aneuploidy & chromosomal microdeletions may provide prognostic information regarding likelihood for success of cancer immunotherapy[3]
Mechanism of action
- cancer cells can elude the immune system by engaging an immune checkpoint on a T-cell, effectively shuting down the T-cell
- checkpoint inhibitors, block that checkpoint & allow T-cells to attack the cancer cells
- TLR9 agonist CMP-001 restores response to checkpoint inhibitor pembrolizumab in 22% of patients with cutaneous melanoma[4]
Comparative biology
- dual immunotherapy with intratumoral delivery of a TLR9 ligand with OX40 activation to ramp up T cell responses led to shrinkage of distant tumors & long-term survival of mice with breast cancer, colon cancer, melanoma & lymphoma[3]
- 87 of 90 mice were cured of cancer
- in the remaining 3 mice, tumors again regressed after a 2nd treatment[2]
Notes
- 2018 Nobel Prize in Physiology or Medicine 2018 awarded jointly to James P. Allison & Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation[6]
More general terms
More specific terms
- adoptive cell transfer
- checkpoint inhibitor therapy
- chimeric antigen-receptor (CAR) T-cell therapy; tisagenlecleucel; CTL019 (Kymriah)
- oncolytic viral therapy
Additional terms
References
- ↑ Young K, Sadoughi S, Sofair A Cancer Immunotherapies May Send Immune System into Overdrive. Physician's First Watch, Dec 5, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
- ↑ 2.0 2.1 Nelson R Cancer Vaccine Works 'Startlingly Well' in Mouse Model. Medscape - Feb 08, 2018 https://www.medscape.com/viewarticle/892447
Sagiv-Barfi I, Czerwinski DK, Levy S Eradication of spontaneous malignancy by local immunotherapy. Sci Transl Med. 2018 Jan 31;10(426) <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29386357 <Internet> http://stm.sciencemag.org/content/10/426/eaan4488.short - ↑ 3.0 3.1 3.2 Kerr DJ Overlooked Biomarker May Predict Cancer Immunotherapy Response. Medscaape. Feb 15, 2018 https://www.medscape.com/viewarticle/892475
Davoli T, Uno H, Wooten EC, Elledge SJ. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science. 2017 Jan 20;355(6322) pii: eaaf8399 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28104840 Free PMC Article - ↑ 4.0 4.1 Bankhead C Drug May Reverse Anti-PD-1 Resistance in Melanoma. Responses in 22% of resistant patients with TLR9 agonist. MedPage Today. April 19, 2018 https://www.medpagetoday.com/meetingcoverage/aacr/72435
Milhem M, et al Intratumoral toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab can reverse resistance to PD-1 inhibition in a phase Ib trial in subjects with advanced melanoma. American Association for Cancer Research (AACR 2018) Abstract CT144 - ↑ 5.0 5.1 Harrison P. Men Do Better than Women on Cancer Immunotherapies. Overall survival improvement twice as great, meta-analysis finds. MedPage Today. May 16, 2018 https://www.medpagetoday.com/hematologyoncology/skincancer/72908
Conforti F, Pala L, Bagnardi V et al Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis. Lancet Oncol 2018; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29778737 https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30261-4/fulltext
Abdel-Rahman O. Does a patient's sex predict the efficacy of cancer immunotherapy? Lancet Oncol 2018; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29778735 https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30270-5/fulltext - ↑ 6.0 6.1 Nobel Prize Press release. Oct 1, 2018 https://www.nobelprize.org/prizes/medicine/2018/press-release/
- ↑ Murphy WJ, Longo DL. The Surprisingly Positive Association Between Obesity and Cancer Immunotherapy Efficacy. JAMA. Published online March 18, 2019. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30882850 https://jamanetwork.com/journals/jama/fullarticle/2728948