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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]
Immunotherapeutic interventions
Generally, cancer immunotherapy refers to immune checkpoint inhibitors and cytokines, adoptive cell therapy, and cancer vaccines.
Immune checkpoint inhibitors
Programmed cell death protein 1 (PD-1)
- Programmed cell death protein 1 (PD-1) is an inhibitory immune checkpoint inhibitor that limits T-cell effector function within tissues, and it is expressed on the surfaces of immune effector cells (T-cells, B cells, NK cells, DCs, and many TILs)and has two known ligands, namely, PD-L1 and PD-L2.
- Anti-PD-1 antibodies (Pembrolizumab, JS001, PDR001, and Nivolumab)
- Anti-PD-L1 antibodies (Atezolizumab and Durvalumab)
Anti-CTLA-4 antibodies (Ipilimumab and Tremelimumab)
- Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a T-cell inhibitory receptor that is expressed on activated CD8+ T cells and CD4+ regulatory T cells that express CD25 and Foxp3. [1]
- Immune checkpoint inhibitors might be combined with targeted therapy (i.e Vascular endothelial growth factor (VEGF) and EGFR (epidermal growth factor receptor) inhibitors)
Adoptive cell therapy
- Adoptive cell therapy is defined as the induction of anti-tumor immune responses via the isolation of highly active and tumor-specific lymphocytes, such as TILs, cytotoxic T lymphocytes (CTLs), Th cells, NK and DC cells.[2]
- Chimeric antigen receptors T-cell-based therapy
- T cell receptors (TCRs)—engineered T cells
Cancer vaccines
- Cancer-testis antigens (CTA) as a vaccine target[3]
- Personalized peptide vaccination (PPV)[4]
- Antigen-presenting cell (APC) and DC-based tumor vaccination[5]
Antibody–drug conjugates (ADC)
- Utilization of monoclonal antibodies that recognize TAAs/TSAs and preferably internalizes when bound to the tumour cells to deliver highly potent cytotoxic agents.[6]
Sacituzumab govitecan
- It is a conjugate of the humanized anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan.
- Each antibody having on average 6.7 molecules of SN-38 attached.
- SN-38 is too toxic to administer directly to patients, but the linkage to an antibody allows the drug to specifically target cells containing Trop-2.
- In in February 2016, Immunomedics announced that sacituzumab govitecan had received an FDA breakthrough therapy designation (a classification designed to expedite the development and review of drugs that are intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition) for the treatment of patients with triple-negative breast cancer who have failed at least two other prior therapies for metastatic disease.[7]
Exosomes
- Exosomes are mall 30–100 nm sized extracellular vesicles
- They are present in many eukaryotic fluids (normal and malignant)
- Particles that encapsulate contents, such as microRNAs.
- Exosome messaging contributes to:[8]
- TME interactions, including:
- Immune suppression and immune escape,
- Invasive growth, adhesion, angiogenesis,
- Radiation resistance, chemo-resistance
- Genetic intercellular exchange,
- May manipulate tumor progression and metastatic cascade
Endoxifen
- Endoxifen is a nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group. It is an active metabolite of tamoxifen and has been found to be effective in patients that have failed previous hormonal therapies (tamoxifen, aromatase inhibitors, and fulvestrant).[9]
Personalized medicine and I-SPY 2 clinical trial
References
- ↑ Leach DR, Krummel MF, Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271 (5256):1734-6. PMID: 8596936
- ↑ June CH (2007) Adoptive T cell therapy for cancer in the clinic. J Clin Invest 117 (6):1466-76. DOI:10.1172/JCI32446 PMID: 17549249
- ↑ Mirandola L, Pedretti E, Figueroa JA, Chiaramonte R, Colombo M, Chapman C et al. (2017) Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy. Oncotarget 8 (43):74378-74390. DOI:10.18632/oncotarget.20102 PMID: 29088794
- ↑ Takahashi R, Toh U, Iwakuma N, Takenaka M, Otsuka H, Furukawa M et al. (2014) Feasibility study of personalized peptide vaccination for metastatic recurrent triple-negative breast cancer patients. Breast Cancer Res 16 (4):R70. DOI:10.1186/bcr3685 PMID: 24992895
- ↑ Zhang P, Yi S, Li X, Liu R, Jiang H, Huang Z et al. (2014) Preparation of triple-negative breast cancer vaccine through electrofusion with day-3 dendritic cells. PLoS One 9 (7):e102197. DOI:10.1371/journal.pone.0102197 PMID: 25036145
- ↑ Panowski S, Bhakta S, Raab H, Polakis P, Junutula JR (2014) Site-specific antibody-drug conjugates for cancer therapy. MAbs 6 (1):34-45. DOI:10.4161/mabs.27022 PMID: 24423619
- ↑ Dizon DS, Krilov L, Cohen E, Gangadhar T, Ganz PA, Hensing TA et al. (2016) Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. J Clin Oncol 34 (9):987-1011. DOI:10.1200/JCO.2015.65.8427 PMID: 26846975
- ↑ Dioufa N, Clark AM, Ma B, Beckwitt CH, Wells A (2017) Bi-directional exosome-driven intercommunication between the hepatic niche and cancer cells. Mol Cancer 16 (1):172. DOI:10.1186/s12943-017-0740-6 PMID: 29137633
- ↑ Hawse JR, Subramaniam M, Cicek M, Wu X, Gingery A, Grygo SB et al. (2013) Endoxifen's molecular mechanisms of action are concentration dependent and different than that of other anti-estrogens. PLoS One 8 (1):e54613. DOI:10.1371/journal.pone.0054613 PMID: 23382923
- ↑ Wu X, Hawse JR, Subramaniam M, Goetz MP, Ingle JN, Spelsberg TC (2009) The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells. Cancer Res 69 (5):1722-7. DOI:10.1158/0008-5472.CAN-08-3933 PMID: 19244106
- ↑ Gingery A, Subramaniam M, Pitel KS, Reese JM, Cicek M, Lindenmaier LB et al. (2014) The effects of a novel hormonal breast cancer therapy, endoxifen, on the mouse skeleton. PLoS One 9 (5):e98219. DOI:10.1371/journal.pone.0098219 PMID: 24853369