Hum Vaccin Immunother. 2013 Jul;9(7):1549-52.

Universal cancer vaccine: an update on the design of cancer vaccines generated from endothelial cells.

Lokhov PG, Balashova EE.

Institute of Biomedical Chemistry RAMS; Moscow, Russia; ZAO BioBohemia; Moscow, Russia.

 

Abstract

Among the potential cancer immunotherapies, vaccination against antigens expressed by endothelial cells lining the tumor vasculature represents one of the most attractive options because this approach may prevent the growth of any solid tumor. Therefore, endothelial cells can be used as a source of antigens for developing a so-called “universal” cancer vaccine. Unfortunately, efficient endothelial cell-based cancer vaccines have not yet been developed because previous approaches utilized direct endothelial cell immunizations which is not effective and can result in the elicitation of autoimmune responses associated with systemic autoimmune vasculitis. Recently, the heterogeneity of the endothelial cell surface was defined using an in vitro system as a means of developing antiangiogenic cancer vaccines. This analysis demonstrated that tumors induced specific changes to the microvascular of human endothelial cell (HMEC) surface thereby providing a basis for the design of endothelial cell-based vaccines that directly target the tumor endothelium. (1) This commentary further describes HMEC heterogeneity from the perspective of designing an endothelial cell-based universal (for the treatment of all solid tumors) cancer vaccine with high immunogenicity that does not pose the risk of eliciting autoimmunity.

KEYWORDS: antiangiogenic cancer vaccine, cell heterogeneity, cell proteomic footprinting, cell surface profiling, microvascular endothelial cells, universal cancer vaccine, vaccine design

PMID: 23571178

 

SUPPLEMENT

 www.biobohemia.com

Immunotherapies that target the tumor vasculature represent one way of preventing tumor growth and metastasis. Included among the various approaches used to elicit immunity against the tumor vasculature is active immunization using endothelial cells (EC). This approach represents the most promising among immunotherapies targeting specific epitopes since cell-based vaccines can target multiple native antigens. Therefore, antigen composition needs to be specified for preparing efficient endothelial cell-based vaccine.

ANTIGENS FOR PREPARING UNIVERSAL CANCER VACCINE

А set of cell surface targets represents the ‘antigenic essence’ of cells and therefore should be represented by cell-based vaccines. Consequently, targeting immune responses against antigens associated with the tumor vasculature (rather than to antigens associated with the vasculature of normal tissues) is based on expression differences between endothelial cell surface antigens in normal tissues and in the tumor vasculature. The universal vaccine described is comprised of cell surface targets collected from the EC stimulated in a definite way with tumor cells. The nature of the cell surface targets are confirmed using cell proteomic footprints (CPF) which represent a ‘snapshot’ of EC surface targets.

The following steps can be employed in the developing a universal cancer vaccine (UCV) comprised of EC surface targets as a means of eliciting immunity against tumor vasculature:

1. Establish a correlation between 2 EC cultures (from 2 patients) by defining their respective CPF.

2. Both EC cultures should be affected in similar manner by tumor-conditioned medium, that is, their surface profiles should be similarly changed. In addition, their CPF should be measured again since CPF similarity is a direct reflection of the degree of change to the cell surface profile following tumor stimulation.

3. Establish a correlation between the efficacy of EC targeting (in the CTA*) and CPF correlation values. The correlation value for the most efficient HMEC targeting should be calculated and autologous target cells from the person receiving the vaccine should be used in the CTA.

4. Tumor-conditioned medium containing different concentrations and/or different growth factor compositions should be used to provide the required growth stimuli for 2 EC cultures to reach the required CPF correlation value. Even if an ideal correlation value is not reached, the actual CPF correlation will show the efficacy of UCV prepared using the obtained antigen composition. If the efficacy is acceptable, autologous EC surface targets should by used for vaccination (with adjuvant).

(* cytotoxicity assays)

According to this protocol a safe and efficacious personal universal vaccine can be developed. Future studies (adjuvant selection and vaccination schedule) for vaccine development are required.

Everybody is invited to collaborate. After approval of the collaboration plan, antigens for preparing universal cancer vaccine will be sent for free.

For details please contact with Dr. Lokhov (lokhovpg@rambler.ru)

Universal Cancer Vaccine

References:

1. Tumor-induced endothelial cell surface heterogeneity directly affects endothelial cell escape from a cell-mediated immune response in vitro. Human Vaccines & Immunotherapeutics. 2013, Volume 9, Issure 1, Pages 198-209. [Pdf file] [PubMed Central]
2. Universal cancer vaccine: An update on the design of cancer vaccines generated from endothelial cells. Human Vaccines & Immunotherapeutics. 2013, Volume 9, Issure 7, Pages 1549-1552. [Pdf file]

3. Cell proteomic footprint. Rapid Communications in Mass Spectrometry, 2009, Volume 23, Issue 5, Pages 680 – 682. [Pdf file]
4. Cellular Cancer Vaccines: an Update on the Development of Vaccines Generated from Cell Surface Antigens“. Journal of Cancer, 2010, Volume 1, Pages 230 – 241. [Pdf file] [PubMed Central]
5. Proteolytically-cleaved fragments of cell surface proteins stimulate a cytotoxic immune response against tumor-activated endothelial cells in vitro. Journal of Cancer Science & Therapy, 2010, Volume 2, Issure 5, Pages 126 – 131. [Pdf file]
6. Proteolytically-cleaved fragments of cell-surface proteins from live tumor cells stimulate anti-tumor immune response in vitro. Journal of Carcinogenesis & Mutagenesis, 2010, Volume 1, Page 103. [Pdf file]
7. Proteomic footprinting of drug-treated cancer cells as a measure of cellular vaccine efficacy for the prevention of cancer recurrence. Molecular & Cellular Proteomics, 2012 February; Volume 11, Issure 2, M111.014480 [Pdf file] [PubMed Central]

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