Continuous DC-CIK Infusions Restore CD8+ Cellular Immunity, Physical Activity and Improve Clinical Efficacy in Advanced Cancer Patients Unresponsive to Conventional Treatments

Abstract

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerateconventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy ofcontinuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and
Methods: A total of381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheralblood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killercells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry toaddress the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteriaand Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimatethe association between cellular infusions and clinical benefits.
Results: An average of 5.7±2.94×109 inducedcells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in thatcytotoxic CD8+CD28+T lymphocytes were increased by 74% and suppressive CD8+CD28-T lymphocytes wereelevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated withimprovement of both patient status and cellular immunity. A median of six infusions were capable of reducingrisk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-foldhigher progression risk (p<0.05) and 1% increase of CD8+CD28- T cell proportion reflecting a 5% higher riskof progression (p<0.05).
Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine inducedkiller cell infusions are capable of recovering cellular immunity, improving patient status and quality of life inthose who are unresponsive to conventional cancer treatment.

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