The Basic And Clinical Research Of Adoptive-cell Immunotherapy

Background: Present study shows that adoptive immunotherapy incomprehensive cancer treatment increasingly important role. Infusion ofautologous CIK cells can effectively remove the malignant tumor of the bloodsystem of minimal residual, and in a variety of solid tumors, CIK cell infusionalso showed inhibition of tumor growth. But for advanced, refractory and relapsedhematologic malignancies, adoptive immune cell therapy is not obvious,especially for patients with high tumor burden in vivo, CIK unable to effectivelykill tumor targeting long-term therapeutic purposes. Based on this, we conducted atwo-part study in this project. First, research extracellular peripheral leukemiacells in vivo with high load AML anti-tumor effects of autologous CIK; then theCD20receptor epitopes modified T cells (CART-20) for the treatment ofrefractory and relapsed DLBCL clinical research. Method:1.The number andphenotypic of CIK cells expanded from11AML patients and10health donors werecompared. Cytotoxicity (against K562and U937cell lines) and cytokine secretion (IL-2,IFN-γ, TNF-α and VEGF) were tested for AML-derived CIK cells, healthy donor-derivedCIK cells and PBMCs from healthy donor. Importantly, we assessed the therapeutic effect ofautologous CIK cell infusions in two AML patients.2. Adult (≥18years) patients withpathologically confirmed diagnose of CD20+DLBCL and active relapsed orrefractory disease were eligible. Patients underwent conditioning chemotherapy ifnecessary for tumor debulking or to maintain disease control. Patientssubsequently received autologous CART-20cells in an escalating dose. Results: 1. CIK cells expressed from recurrent or refractory AML patients have great potential forthe treatment for refractory and relapsed AML.2. Seven patients were enrolled, and sixreceived conditioning chemotherapies before autologous CART cell infusion fordebulking. One of the two patients with no bulky tumor obtained a13-monthdurable and ongoing complete remission by cell infusion only, and anotherattained a6-month tumor regression. Four of five patients with bulky tumorburden were evaluable for clinical efficacy, three of which attained3-to6-monthtumor regression. Delayed toxicities related to cell infusion are directly correlatedto tumor burden and tumor-harboring sites, and mainly included cytokine releasesymptoms, tumor lysis symptoms, massive hemorrhage of the alimentary tract andaggressive intrapulmonary inflammation surrounding extranodal lesions.Conclusions: Adoptive immune cell therapy may take possible to obtain effectivedisease remission for refractory and relapsed AML and DLBCL.