1. Ex vivo isolation, expansion and bioengineering of CCR7+CD95-/or CD62L+CD45RA+ tumor infiltrating lymphocytes from acute myeloid leukemia patients’ bone marrow
- Author
-
Samiksha Wasnik, Jeffrey Xiao, Chien-Shing Chen, Do Hyun Kim, Mark E. Reeves, David J. Baylink, Ashley Howard, Olivia L. Francis, Hector Moz, Saied Mirshahidi, Huynh Cao, Yi Xu, and Guido Marcucci
- Subjects
Male ,Cancer Research ,medicine.medical_treatment ,Cell Separation ,Mice ,FACS, flow cytometry ,T-Lymphocyte Subsets ,hemic and lymphatic diseases ,PD-1 ,Medicine ,L-Selectin ,AML, acute myeloid leukemia ,RC254-282 ,biology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Myeloid leukemia ,hemic and immune systems ,Middle Aged ,Adoptive Transfer ,Adoptive cell therapy ,CAR-T ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,BMMNC, bone marrow mononuclear cells ,CD95 ,Heterografts ,Female ,Immunotherapy ,Adult ,Original article ,Receptors, CCR7 ,CD3 ,T cell ,chemical and pharmacologic phenomena ,Bioengineering ,Bone Marrow Cells ,Peripheral blood mononuclear cell ,Lymphocytes, Tumor-Infiltrating ,CD62L ,CD45RA ,Animals ,Humans ,Bone marrow ,fas Receptor ,Aged ,Programmed cell death protein 1 ,Acute myeloid leukemia ,Tumor-infiltrating lymphocytes ,business.industry ,HSCs, hematopoietic stem cells ,Naïve T ,Interleukin ,IL, interleukin ,TILs, tumor-infiltrating lymphocytes ,biology.protein ,Cancer research ,Tumor-Infiltrating Lymphocytes ,BM, bone marrow ,Leukocyte Common Antigens ,business ,Ex vivo ,CCR7 - Abstract
T cell based immunotherapies can be applicable to acute myeloid leukemia (AML). Therefore, the selection of optimal T cells, cell manufacturing, and therapeutic T cell engineering are essential for the development of effective adoptive T cell therapies for AML. Autologous tumor-infiltrating lymphocytes (TILs) have been in clinical trials to treat solid malignancies. Herein, we assessed whether TILs can be isolated from the bone marrow (BM) of AML patients, expanded ex vivo and utilized as a novel therapeutic strategy for AML. To this end, firstly we analyzed the immunophenotypes of a series of primary BM samples from AML patients (N = 10) by flow cytometry. We observed a variable amount of CD3+ TILs (range ∼2.3–∼32.6% of mononuclear cells) among BM samples. We then developed a novel protocol that produced a three-log ex vivo expansion of TILs isolated from AML patient BM (N = 10) and peripheral blood (PB) (N = 10), including from patients with a low number of CD3+ T cells, within 3, 4 weeks. Further, we identified previously described naïve T cells (CCR7+CD95-/or CD62L+CD45RA+) in AML BM and PB samples, which seemed to be required for a successful TILs ex vivo expansion. Finally, we showed that the expanded TILs could: (1) cause cytotoxicity to autologous AML blasts ex vivo (90.6% in control without T cell treatment vs. 1.89% in experimental groups with PB derived T cells and 1.77% in experimental groups with BM derived TILs, p
- Published
- 2021