BlueCross BlueShield of Tennessee Medical Policy Manual

Adoptive Immunotherapy


Adoptive immunotherapy or adoptive cellular therapy is the administration of an individuals own (autologous) or donor (allogeneic) anti-tumor lymphocytes as a proposed treatment for various malignancies. Both nonspecific and specific lymphocyte activation are used therapeutically.

The spontaneous regression of certain cancers support the idea that an individual’s immune system is sometimes capable of delaying tumor progression, and on rare occasions, can eliminate the tumor. These observations have led to research interested in a variety of immunologic therapies designed to stimulate an individual’s own immune system. These therapies can be categorized into active specific (e.g., increasing select populations of cytotoxic T lymphocytes with specific reactivity to tumor antigens), active non-specific (i.e., the use of interleukin-2 to increase the number of activated lymphocytes), and passive immunotherapy (i.e., transfer of specific immune cells such as cytotoxic T-lymphocytes or lymphokine-activated killer cells to produce antibodies). Protocols vary, but usually include these common steps:

  1. Lymphocyte harvesting (either from peripheral blood or from tumor biopsy)

  2. Propagation of tumor-specific lymphocytes in vitro using various immune modulators

  3. Selection of lymphocytes with reactivity to tumor antigens with enzyme-linked immunosorbent assay

  4. Lymphodepletion of the host with immunosuppressive agents

  5. Adoptive transfer (ie, transfusion) of lymphocytes back into the tumor-bearing host




The evidence for adoptive immunotherapy in individuals who have various types of cancer includes randomized controlled trials (RCTs), nonrandomized comparative studies, and uncontrolled trials. The impact of adoptive immunotherapy on patient outcomes (e.g., increased survival, improved quality of life) has yet to be clarified.


BlueCross BlueShield Association. Evidence Positioning System. (7:2018). Adoptive immunotherapy (8.01.01) Retrieved November 16, 2018 from (84 articles and/or guidelines reviewed)

Lee, J., Lee, J., Lim, Y., Yeon-Suk, L., Song, T., Yu, S., t. al. (2015) Adjuvant immunotherapy with autologous cytokine-induced killer cells for hepatocellular carcinoma. Gastroenterology 2015; Vol. 148, No. 7:1383-1391. (Level 2 evidence)

Li, Y., Zhao, L., Wu, J., Qu, C., Song, Q., & Wang, R. (2016). Cytokine-induced killer cell infusion combined with conventional treatments produced better prognosis for hepatocellular carcinoma patients with Barcelona clinic liver cancer B or earlier state: A systematic review and meta-analysis. Cytotherapy, 18 (12), 1525-1531.  Abstract retrieved December 28, 2016 from PubMed database.

Liu, L., Zhang, W., Qi, X, Li, H., Yu, J., Wei, S., et al. (2012). Randomized study of autologous cytokine-induced killer cell immunotherapy in metastatic renal carcinoma. Clinical Cancer Research, 18 (6), 1751-1759. (Level 2 Evidence)

Maciocia, P., Wawrzyniecka, P., Philip, B., Ricciardelli, I., Akarca, A., Onuoha, S., et al. (2017, December) Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nature Medicine, 23(12), 1416-1423. Abstract retrieved January 10, 2018 from PubMed database.

Mi, D., Ren, W., & Yang, K. (2016). Adoptive immunotherapy with interleukin-2 & induced killer cells in non-small cell lung cancer: a systematic review & meta-analysis. Indian Journal of Medical Research, 143 (Suppl 1), S1-S10. (Level 1 evidence)

National Comprehensive Cancer Network. (2018, March). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Acute lymphoblastic leukemia, version 1.2018. Retrieved November 19, 2018 from

National Comprehensive Cancer Network. (2018, October). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). B-cell lymphomas, version 5.2018. Retrieved November 19, 2018 from

Qian, H., Wang, H., Guan, X., Yi, Z., Ma, F. (2016). Adoptive immunotherapy combined chemoradiotherapy for non-small-cell lung cancer: a meta-analysis. Anticancer Drugs, 27 (5), 433-438. Abstract retrieved December 28, 2016 from PubMed database.

Shen, D., Liu, Z., Xu, J., Xu, F., Lin, Q., Lin, F., & Mao, W. (2016). Efficacy of adoptive cellular therapy in patients with gastric cancer: a meta-analysis. Immunotherapy, 8 (8), 971-981. Abstract retrieved December 28, 2016 from PubMed database.

Tang, X., Liu, T., Zhang, B. (2013). Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis. PLoS One, 8 (5), e62847. (Level 2 evidence)

Xie, F., Zhang, X., Li, H., Zheng, T., Xu, F., Shen, R., et al (2012). Adoptive immunotherapy in postoperative hepatocellular carcinoma: A systematic review. PLoS One, 7 (8), e42879. (Level 1 evidence)

Zeng, Y., Ruan, W., He, J. (2016). Adoptive immunotherapy in postoperative non-small-cell lung cancer: a systematic review and meta-analysis. PLoS One, 11 (9), e0162630. (Level 1 evidence)




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