Adoptive cell transfer

Adoptive cell transfer can refer to the transfer of cells, most commonly immune-derived cells, back into the same patient or into a new recipient host with the goal of transferring the immunologic functionality and characteristics into the new host. If possible, use of autologous cells helps the recipient by minimizing GVHD issues. For isolation of immune cells for adpotive transfer, a phlebotomist draws blood into tubes containing anticoagulant and the PBM (buffy coat) cells are isolated, typically by density barrier centrifugation. In T cell-based therapies, these cells are expanded in vitro using cell culture methods relying heavily on the immunomodulatory action of interleukin-2 and returned to the patient in large numbers intravenously in an activated state. Anti-CD3 antibody is commonly used to promote the proliferation of T cells in culture. Research into interleukin-21 suggests it may also play an important role in enhancing the efficacy of T cell based therapies prepared in vitro. An emerging treatment modality for various diseases is the transfer of stem cells to achieve therapeutic effect. Clinically, this approach has been exploited to transfer either immune-promoting or tolerogenic cells (often lymphocytes) to patients to either enhance immunity against viruses and cancer[1] [2] [3] or to promote tolerance in the setting of autoimmune disease,[4] such as Type I diabetes or rheumatoid arthritis. Cells used in adoptive therapy may be genetically modified using recombinant DNA technology to achieve any number of goals. One example of this in the case of T cell adoptive therapy is the addition of chimeric antigen receptors, or CARs, to redirect the specificity of cytotoxic and helper T cells.

Uses

To treat cancer

The adoptive transfer of autologous tumor infiltrating lymphocytes (TIL)[5][6][7] or genetically re-directed peripheral blood mononuclear cells[8][9] has been used to successfully treat patients with advanced solid tumors, including melanoma and colorectal carcinoma, as well as patients with CD19-expressing hematologic malignancies[10]

To induce tolerance in autoimmune disease

e.g. Transfer regulatory T cells to treat Type 1 diabetes and others.[4]

References

  1. Gattinoni L, Powell DJ, Rosenberg SA, Restifo NP (May 2006). "Adoptive immunotherapy for cancer: building on success". Nature Reviews Immunology 6 (5): 383–93. doi:10.1038/nri1842. PMC 1473162. PMID 16622476.
  2. June CH (June 2007). "Adoptive T cell therapy for cancer in the clinic". The Journal of Clinical Investigation 117 (6): 1466–76. doi:10.1172/JCI32446. PMC 1878537. PMID 17549249.
  3. Schmitt TM, Ragnarsson GB, Greenberg PD (October 2009). "T Cell Receptor Gene Therapy for Cancer". Human Gene Therapy 20 (11): 1240–8. doi:10.1089/hum.2009.146. PMC 2829456. PMID 19702439.
  4. 4.0 4.1 Riley JL, June CH, Blazar BR (May 2009). "Human T Regulatory Cells as Therapeutic Agents: Take a Billion or So of These and Call Me in the Morning". Immunity 30 (5): 656–65. doi:10.1016/j.immuni.2009.04.006. PMC 2742482. PMID 19464988.
  5. Besser MJ, Shapira-Frommer R, Treves AJ, et al. (May 2010). "Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients" Clin. Cancer Res 16 (9) 2646–55. .doi:10.1158/1078-0432.CCR-10-0041 PMID 20406835
  6. Dudley ME, Wunderlich JR, Robbins PF et al. (October 2002). "Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes". Science 298 (5594): 850–4. doi:10.1126/science.1076514. PMC 1764179. PMID 12242449.
  7. Dudley ME, Wunderlich JR, Yang JC et al. (April 2005). "Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic Melanoma". Journal of Clinical Oncology 23 (10): 2346–57. doi:10.1200/JCO.2005.00.240. PMC 1475951. PMID 15800326.
  8. Johnson LA, Morgan RA, Dudley ME et al. (July 2009). "Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen". Blood 114 (3): 535–46. doi:10.1182/blood-2009-03-211714. PMC 2929689. PMID 19451549.
  9. Morgan RA, Dudley ME, Wunderlich JR et al. (October 2006). "Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes". Science 314 (5796): 126–9. doi:10.1126/science.1129003. PMC 2267026. PMID 16946036.
  10. Kalos M, Levine BL, Porter DL et al. (August 2011). "T Cells with Chimeric Antigen Receptors Have Potent Antitumor Effects and Can Establish Memory in Patients with Advanced Leukemia". Science Translational Medicine 3 (95): 95ra73. doi:10.1126/scitranslmed.3002842. PMC 3393096. PMID 21832238.