Autologous T-Cell Transplantation and the Immunotherapy of Residual Disease in Breast Cancer: Pilot Study of Vaccine-Driven T-Cell Expansion in Patients Treated With Dose-Intensive Chemotherapy

Neoplasm Metastasis Clinical Trial

Official title: Pilot Study of Autologous T Cells and/or IL-2 for the Enhancement of Immune Reconstitution After Dose-Intensive Chemotherapy for Breast Cancer

Status Completed

Clinical Trial Summary

The ability of chemotherapy to cure cancer, including breast cancer, has been limited by drug resistant residual tumor cells remaining after chemotherapy that generally result in relapse. Additional therapeutic strategies to eradicate these residual tumor cells are needed. The augmentation of specific anti-tumor immune responses, such as those mediated by T-cells, might represent such an additional strategy for the control or elimination of residual tumor cells. This approach might be especially effective if T-cell mediated responses were enhanced during both the period of T-cell repopulation that follows acute T-cell depletion and in the setting of minimal residual tumor burden present after dose intensive chemotherapy. Such chemotherapy is known to result in severe T-cell depletion. This pilot study has been designed to examine the feasibility of combining dose intensive chemotherapy with interventions aimed at the reconstitution of T-cell immunity. Metastatic or adjuvant breast cancer patients who have received dose intensive chemotherapy will subsequently receive a combination of autologous chemotherapy-naive T-cells, a patient-specific tumor antigen vaccine, and recombinant human interleukin-2. These interventions will be assessed for their ability to modulate T-cell number, T-cell function, and T-cell specificity during the period of T-cell repopulation. Such modulation may result in the effective reconstitution of generalized T-cell immunity with the generation of vaccine-specific anti-tumor T-cell responses.

Clinical Trial Description

The process of T cell immune reconstitution post-chemotherapy in breast cancer patients is impaired. Such a deficit in T cell immunity likely represents an important obstacle to tumor vaccine therapy in breast cancer patients. In an attempt to enhance T cell immune reconstitution, we have administered cryopreserved T cells and interleukin-2 to breast cancer patients post-chemotherapy. Initial data from the first 13 patients enrolled on this study suggests that the administration of T cells and IL-2 resulted in improved T cell reconstitution relative to untreated patients or patients receiving only IL-2. Importantly, recipients of the combination of T cells and IL-2 had an enhanced recovery of CD4+CD45RA+ T cells; because this T cell subset represents a naive T cell phenotype that generally maintains a capacity to respond to antigen, enhanced regeneration of this population may result in improved immune function and may allow for a more successful immune response to tumor vaccines. It will be important to now evaluate what effect T cell administration alone (without IL-2 treatment) has on immune reconstitution post-chemotherapy. Determination of the relative benefits of T cell and/or cytokine administration on T cell recovery post-chemotherapy may assist in the development of breast cancer vaccine protocols where a T cell-mediated immune response may be necessary for optimal response to the vaccine. ;

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasm
• Breast Neoplasms
• Neoplasm Metastasis
• Neoplasms

• NCT number: NCT00001440
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: July 1995
• Completion date: January 2002