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Development of vaccines against self-antigens: the p53 paradigm
Sunil Chada1, Abner Mhashilkar, Jack A Roth
1Introgen Therapeutics Inc, 2250 Holcombe Boulevard, Houston, TX 77030, USA. s.chada@introgen.com
Abstract:
Active immunotherapy using dendritic cells (DCs) to deliver tumor antigens has generated considerable excitement among oncologists worldwide. Although most tumor antigens used in immunotherapeutic approaches are tumor-associated, often, little is known about the underlying biology of the target. Here, we review the use of 'obligate' tumor antigens, where antigen expression is a prerequisite for tumor formation or maintenance. The prototype for this class of antigens is the p53 tumor antigen, which is mutated in > 50% of human malignancies. The direct involvement of p53 in the malignant transformation of tumors makes it an attractive target for immunotherapy. p53-Reactive antibodies have been found in patients with various types of cancer, demonstrating that the human immune system can recognize and respond to tumor-associated p53. Extensive preclinical experimentation has now validated the translation of p53-expressing DCs into a clinical setting. Clinical trials are ongoing to evaluate the safety and antitumor responses elicited by DCs transduced with adenoviral-p53 in cancer patients.
Insights
Active immunotherapy utilizes dendritic cells (DCs) to target tumor antigens. Targeting obligate tumor antigens like p53, essential for cancer, shows promise in ongoing clinical trials for effective cancer treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Active immunotherapy with dendritic cells (DCs) is a promising cancer treatment strategy.
- Most tumor antigens are tumor-associated, with limited understanding of their biological roles.
- Obligate tumor antigens are crucial for tumor formation or maintenance, making them ideal therapeutic targets.
Purpose of the Study:
- To review the therapeutic potential of obligate tumor antigens in cancer immunotherapy.
- To highlight the p53 tumor antigen as a prototype for this class of antigens.
- To discuss the translation of p53-based dendritic cell immunotherapy into clinical practice.
Main Methods:
- Review of existing literature on obligate tumor antigens and p53.
- Analysis of preclinical data supporting p53-expressing DC immunotherapy.
- Examination of ongoing clinical trials evaluating p53-transduced DCs.
Main Results:
- The p53 tumor antigen is mutated in over 50% of human cancers and is critical for malignant transformation.
- The human immune system can recognize and respond to tumor-associated p53, as evidenced by p53-reactive antibodies in cancer patients.
- Preclinical studies demonstrate the efficacy of p53-expressing DCs for cancer immunotherapy.
Conclusions:
- Obligate tumor antigens, exemplified by p53, represent a viable strategy for active cancer immunotherapy.
- p53-expressing dendritic cell therapy has been validated in preclinical models and is currently under clinical investigation.
- Ongoing clinical trials will assess the safety and efficacy of adenoviral-p53 transduced DCs in cancer patients.