Tumor lysate-loaded biodegradable microparticles as cancer vaccines

Abstract

Cancer vaccines that use tumor lysate (TL) as a source of tumor-associated antigens (TAAs) have significant potential for generating therapeutic anti-tumor immune responses. Vaccines encompassing TL bypass the limitations of single antigen vaccines by simultaneously stimulating immunity against multiple TAAs, thereby broadening the repertoire of TAA-specific T-cell clones available for activation. Administration of TL in particulate form, such as when encapsulated in biodegradable microparticles, increases its immunostimulatory capacity and produces more robust immune responses than when TL is given in soluble form. These effects can be further enhanced by co-administering TL with adjuvants. A number of recent studies using polymeric microparticle delivery of TL, with or without adjuvants, have produced promising results in preclinical studies. In this review, we will discuss current experimental approaches involving TL being pursued in the oncoimmunology field, and comment on strategies such as combining specific chemotherapeutic agents with TL microparticle delivery that may eventually lead to improved survival outcomes for cancer patients.

Keywords::

• biodegradable polymers
• cancer
• microparticles
• tumor lysate
• vaccine

Financial & competing interests disclosure

The authors were supported by the American Cancer Society (RSG-09-015-01-CDD), and the National Cancer Institute at the National Institutes of Health (1R21CA13345-01/1R21CA128414-01A2/UI Mayo Clinic Lymphoma SPORE). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Tumor cells express a blend of defined, and in all likelihood, undefined tumor-associated antigens (TAAs) which could be potential targets for the host’s immune response.

• Tumor lysate (TL), as the antigenic component of a cancer vaccine, can provide multiple TAAs as immune targets thereby decreasing the possibility of immune evasion by the tumor through epitope loss or through intratumoral heterogeneity.

• TL vaccines involving either autologous or allogeneic TLs increase the patient eligibility rate over single TAA-based vaccines by obviating the restriction imposed by HLA phenotypes.

• Particulated delivery of TL using biodegradable polymer formulations provides many benefits that include promotion of co-delivery of TL and adjuvant to the same dendritic cell (DC).

• Different types of biodegradable polymers could potentially be used as delivery systems for TL, however at this stage poly(lactic-co-glycolic acid) has been the only polymer to have been studied extensively.