Radioimmunotherapy of experimental human metastatic melanoma with melanin-binding antibodies and in combination with dacarbazine

Ekaterina Revskaya, Artemio M. Jongco, Rani S. Sellers, Robertha C. Howell, Wade Koba, Allan J. Guimaraes, Joshua D. Nosanchuk, Arturo Casadevall, Ekaterina Dadachova

Research output: Contribution to journalArticle

Abstract

Purpose: Melanin has emerged as an attractive target for radioimmunotherapy (RIT) of melanoma, and a radiolabeled monoclonal antibody (mAb) 6D2 to melanin is currently in clinical evaluation. We investigated two approaches to improve the targeting of radiation to tumors using melanin-binding mAbs: (a) the use of an additional mAb to melanin could provide information on whether using antibodies to melanin can serve as a general approach to development of therapeutics for melanoma, and (b) as melanin targeting involves the antibody binding to extracellular melanin released from necrotic melanoma cells, we hypothesized that the administration of a chemotherapeutic agent followed by RIT would facilitate the delivery of radiation to the tumors due to the increased presence of free melanin. Experimental Design: We evaluated the therapeutic efficacy of two melanin-binding IgM mAbs labeled with 188Re (6D2 and 11B11). We compared the efficacy of RIT with 188Re-6D2 to chemotherapy with dacarbazine (DTIC) and to combined chemotherapy and RIT in human metastatic melanoma-bearing nude mice. Results: Therapeutic efficacy of 188Re-labeled 6D2 and 11B11 was comparable despite differences in their affinity and binding site numbers. Comparison of chemotherapy with DTIC and RIT revealed that RIT was more effective in slowing tumor growth in mice. Administration of DTIC followed by RIT was more effective than either modality alone. Conclusions: These results provide encouragement for the development of RIT for melanoma with melanin-binding mAbs and suggest that combining chemotherapy and RIT may be a promising approach for the treatment of metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)2373-2379
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number7
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

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Radioimmunotherapy
Dacarbazine
Melanins
Melanoma
Antibodies
Drug Therapy
Monoclonal Antibodies
Radiation
Neoplasms
Therapeutics
Nude Mice
Immunoglobulin M
Research Design
Binding Sites

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Revskaya, E., Jongco, A. M., Sellers, R. S., Howell, R. C., Koba, W., Guimaraes, A. J., ... Dadachova, E. (2009). Radioimmunotherapy of experimental human metastatic melanoma with melanin-binding antibodies and in combination with dacarbazine. Clinical Cancer Research, 15(7), 2373-2379. https://doi.org/10.1158/1078-0432.CCR-08-2376

Radioimmunotherapy of experimental human metastatic melanoma with melanin-binding antibodies and in combination with dacarbazine. / Revskaya, Ekaterina; Jongco, Artemio M.; Sellers, Rani S.; Howell, Robertha C.; Koba, Wade; Guimaraes, Allan J.; Nosanchuk, Joshua D.; Casadevall, Arturo; Dadachova, Ekaterina.

In: Clinical Cancer Research, Vol. 15, No. 7, 01.04.2009, p. 2373-2379.

Research output: Contribution to journalArticle

Revskaya, E, Jongco, AM, Sellers, RS, Howell, RC, Koba, W, Guimaraes, AJ, Nosanchuk, JD, Casadevall, A & Dadachova, E 2009, 'Radioimmunotherapy of experimental human metastatic melanoma with melanin-binding antibodies and in combination with dacarbazine', Clinical Cancer Research, vol. 15, no. 7, pp. 2373-2379. https://doi.org/10.1158/1078-0432.CCR-08-2376
Revskaya, Ekaterina ; Jongco, Artemio M. ; Sellers, Rani S. ; Howell, Robertha C. ; Koba, Wade ; Guimaraes, Allan J. ; Nosanchuk, Joshua D. ; Casadevall, Arturo ; Dadachova, Ekaterina. / Radioimmunotherapy of experimental human metastatic melanoma with melanin-binding antibodies and in combination with dacarbazine. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 7. pp. 2373-2379.
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AU - Howell, Robertha C.

AU - Koba, Wade

AU - Guimaraes, Allan J.

AU - Nosanchuk, Joshua D.

AU - Casadevall, Arturo

AU - Dadachova, Ekaterina

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