Adoptive immunotherapy against sarcomas

Abstract

Preclinical findings and initial clinical reports showed the potentialities and drawbacks of different adoptive immunotherapy strategies. The expansion of tumor infiltrating lymphocytes is difficult to be reproduced outside melanoma. Genetically redirected T cells appear to be a promising option and initial reports are encouraging against patients with sarcomas. Adoptive immunotherapy with MHC-unrestricted effectors such as NK, CIK or γδ T cells has recently shown great preclinical potential in sarcoma setting and biologic features that may favor clinical transferability. Combination of different immunotherapy approaches and integration with conventional treatments appear to be key issues for successful designing of next clinical trials.

Cytokines induced killer cells produced in good manufacturing practices conditions: identification of the most advantageous and safest expansion method in terms of viability, cellular growth and identity

“…The clinical translation of adoptive immunotherapy with CIK cells as treatment for patients with solid tumors is currently the object of clinical trials and their number has increased in recent years [ 1 ]. They can be classically expanded starting from peripheral blood mononuclear cells (PBMCs) [ 2 , 3 ] but may also be generated from bone marrow (BM) or umbilical cord blood precursors [ 4 ].…”

T-Cell-Based Immunotherapy for Osteosarcoma: Challenges and Opportunities

“…Clinical application of T cell therapy for osteosarcoma faces several obstacles before it can be introduced into clinical practice. These include: (1) required production with stringent GMP (good manufacturing practice) procedures in dedicated facilities; (2) necessity of lymphodepleting preparative treatment; and (3) advocate combination of different immunotherapy approaches and integration with conventional treatments ( 64 ).…”

“…The use of adoptive γδ T cell transfer in cancer immunotherapy is a new treatment, especially with regard to osteosarcomas. The main advantages and disadvantages of adoptive γδ T cell transfer immunotherapy are summarized below: (1) it is MHC-independent (all patients may benefit); (2) it is not affected by immune-escape MHC-downregulation; (3) it is not restricted to any precise sarcoma histotype; (4) it has high rates of ex vivo expansion with simple protocols; (5) it has limited persistence in vivo ; and (6) its recognition is limited to extracellular targets ( 64 ). Unlike αβ T cells, γδ T cells can naturally recognize tumor antigens in an MHC-independent manner without antigen processing.…”

Adoptive immunotherapy against ovarian cancer

“…NK cells activation is dependent upon the activation of costimulatory NK cell receptors (NKR), including NKG2D, DNAX accessory molecule-1 (DNAM-1), 2B4, NTB-A, CRACC, CD2, CD59, NKp80, CD94/NKG2C, and of the natural cytotoxicity receptors (NCR: NKp30, NKp44, and NKp46) [ 46 ]. NK cells have a well-known capacity to kill a wide variety of tumors, like sarcoma and leukemia [ 47 – 49 ] but in ovarian cancer disease the efficacy of NK cells to kill tumor is not clear [ 1 ]. Carlsten et al have shown that NKs derived from healthy donor can recognize and kill in vitro ovarian carcinoma cells, isolated from peritoneal effusions, through the activation of DNAM-1 signaling with complementary contributions of NKG2D and NCR receptors [ 46 ].…”