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cancer immunotherapy

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]

Related

checkpoint inhibitor; immune checkpoint inhibitor; PD-1/PD-L1 inhibitor

Specific

adoptive cell transfer checkpoint inhibitor therapy chimeric antigen-receptor (CAR) T-cell therapy; tisagenlecleucel; CTL019 (Kymriah) oncolytic viral therapy

General

biotherapy (immunotherapy)

References

  1. 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. 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) PMID: 29386357 http://stm.sciencemag.org/content/10/426/eaan4488.short
  3. 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: 28104840 Free PMC Article
  4. 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. 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: 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: 29778735 https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30270-5/fulltext
  6. Nobel Prize Press release. Oct 1, 2018 https://www.nobelprize.org/prizes/medicine/2018/press-release/
  7. Murphy WJ, Longo DL. The Surprisingly Positive Association Between Obesity and Cancer Immunotherapy Efficacy. JAMA. Published online March 18, 2019. PMID: 30882850 https://jamanetwork.com/journals/jama/fullarticle/2728948