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Cellular immunotherapy and autologous transplantation for hematologic malignancy
K A Margolin1, R S Negrin, K K Wong
1Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California 91010, USA.
Immunological Reviews
|June 1, 1997
Summary
Researchers are enhancing autologous transplants by boosting the graft-versus-tumor effect. Strategies include using cytokine-induced killer (CIK) cells and genetically modifying antigen-presenting cells (APCs) to improve cancer immunotherapy outcomes.
Area of Science:
- Immunology
- Transplantation Biology
- Cancer Therapy
Background:
- Allogeneic transplantation success relies on graft immunotherapeutic effects, unlike autologous transplantation, which has higher relapse rates due to the lack of this effect.
- Developing an autologous graft-versus-tumor effect is crucial for improving autologous transplant efficacy and reducing relapse.
- Current research focuses on augmenting the immunologic activity of the graft in autologous transplantation.
Purpose of the Study:
- To explore strategies for enhancing the immunologic activity of autologous grafts.
- To introduce an autologous graft-versus-tumor effect to decrease relapse rates after autologous transplantation.
- To investigate novel methods for generating potent anti-tumor immune responses within autologous transplants.
Main Methods:
- Interleukin-2 (IL-2) activation of marrow followed by post-transplant IL-2 infusions.
- Development of cytokine-induced killer (CIK) cells for potent antitumor activity.
- Gene transfer into antigen-presenting cells (APCs) using adeno-associated virus (AAV) vectors to generate peptide-specific T cells.
Main Results:
- Successful generation of highly efficient CIK cells with broad antitumor activity.
- Adeno-associated virus (AAV) vector-mediated gene transfer into human monocytes and macrophages resulted in high expression of transduced genes.
- Demonstrated potential for genetically modified APCs to enhance specific immune responses to tumor antigens.
Conclusions:
- Augmenting graft immunologic activity, through methods like CIK cells and gene-modified APCs, holds promise for improving autologous transplantation.
- These strategies aim to establish an autologous graft-versus-tumor effect, thereby reducing relapse rates.
- Further research into genetically modified APCs can potentiate specific anti-tumor immune responses, increasing the therapeutic efficacy of autologous transplantation.