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Eradication of melanomas by targeted elimination of a minor subset of tumor cells.

ABSTRACT: Proceeding on the assumption that all cancer cells have equal malignant capacities, current regimens in cancer therapy attempt to eradicate all malignant cells of a tumor lesion. Using in vivo targeting of tumor cell subsets, we demonstrate that selective elimination of a definite, minor tumor cell subpopulation is particularly effective in eradicating established melanoma lesions irrespective of the bulk of cancer cells. Tumor cell subsets were specifically eliminated in a tumor lesion by adoptive transfer of engineered cytotoxic T cells redirected in an antigen-restricted manner via a chimeric antigen receptor. Targeted elimination of less than 2% of the tumor cells that coexpress high molecular weight melanoma-associated antigen (HMW-MAA) (melanoma-associated chondroitin sulfate proteoglycan, MCSP) and CD20 lastingly eradicated melanoma lesions, whereas targeting of any random 10% tumor cell subset was not effective. Our data challenge the biological therapy and current drug development paradigms in the treatment of cancer.

SUBMITTER: Schmidt P

PROVIDER: S-EPMC3038763 | biostudies-other | 2011 Feb

REPOSITORIES: biostudies-other

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Eradication of melanomas by targeted elimination of a minor subset of tumor cells.

Schmidt Patrick P Kopecky Caroline C Hombach Andreas A Zigrino Paola P Mauch Cornelia C Abken Hinrich H

Proceedings of the National Academy of Sciences of the United States of America 20110131 6

Proceeding on the assumption that all cancer cells have equal malignant capacities, current regimens in cancer therapy attempt to eradicate all malignant cells of a tumor lesion. Using in vivo targeting of tumor cell subsets, we demonstrate that selective elimination of a definite, minor tumor cell subpopulation is particularly effective in eradicating established melanoma lesions irrespective of the bulk of cancer cells. Tumor cell subsets were specifically eliminated in a tumor lesion by adopt ...[more]

PMID: 21282657

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Project description:BackgroundInfectious diseases elimination and eradication have become important areas of focus for global health and countries. Due to the substantial up-front investments required to eliminate and eradicate, and the overall shortage of resources for health, economic analysis can inform decision making on whether elimination/eradication makes economic sense and on the costs and benefits of alternative strategies. In order to draw lessons for current and future initiatives, we review the economic literature that has addressed questions related to the elimination and eradication of infectious diseases focusing on: why, how and for whom?MethodsA systematic review was performed by searching economic literature (cost-benefit, cost-effectiveness and economic impact analyses) on elimination/eradication of infectious diseases published from 1980 to 2013 from three large bibliographic databases: one general (SCOPUS), one bio-medical (MEDLINE/PUBMED) and one economic (IDEAS/REPEC).ResultsA total of 690 non-duplicate papers were identified from which only 43 met the inclusion criteria. In addition, only one paper focusing on equity issues, the "for whom?" question, was found. The literature relating to "why?" is the largest, much of it focusing on how much it would cost. A more limited literature estimates the benefits in terms of impact on economic growth with mixed results. The question of how to eradicate or eliminate was informed by an economic literature highlighting that there will be opportunities for individuals and countries to free-ride and that forms of incentives and/or disincentives will be needed. This requires government involvement at country level and global coordination. While there is little doubt that eliminating infectious diseases will eventually improve equity, it will only happen if active steps to promote equity are followed on the path to elimination and eradication.ConclusionThe largest part of the literature has focused on costs and economic benefits of elimination/eradication. To a lesser extent, challenges associated with achieving elimination/eradication and ensuring equity have also been explored. Although elimination and eradication are, for some diseases, good investments compared with control, countries' incentives to eliminate do not always align with the global good and the most efficient elimination strategies may not prioritize the poorest populations. For any infectious disease, policy-makers will need to consider realigning contrasting incentives between the individual countries and the global community and to assure that the process towards elimination/eradication considers equity.

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Eradication of melanomas by targeted elimination of a minor subset of tumor cells.

Publications

Eradication of melanomas by targeted elimination of a minor subset of tumor cells.

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