A phase I study of anti‐GD3 ganglioside monoclonal antibody R24 and recombinant human macrophage‐colony stimulating factor in patients with metastatic melanoma Journal Article

  

Authors:	Minasian, L. M.; Yao, T. J.; Steffens, T. A.; Scheinberg, D. A.; Williams, L.; Riedel, E.; Houghton, A. N.; Chapman, P. B.
Article Title:	A phase I study of anti‐GD3 ganglioside monoclonal antibody R24 and recombinant human macrophage‐colony stimulating factor in patients with metastatic melanoma
Abstract:	Background. Macrophages activated by macrophage‐colony stimulating factor (M‐CSF) are potent immune effector cells and can mediate both in vitro cytotoxicity and antitumor effects in vivo. A Phase I trial combining M‐CSF with R24, a mouse monoclonal antibody against GD3 ganglioside that has been shown to localize to melanoma tumors, induce inflammation at tumor sites, and result in major tumor responses in some patients with melanoma was performed. Methods. Nineteen patients with metastatic melanoma received a 14‐day continuous intravenous infusion of 80 80μg/kg/day of recombinant human M‐CSF. R24 was administered daily by intravenous infusion on days 6‐10 at doses of 1, 3, 10, 30, and 50 μg/m2/day. Results. All patients developed pruritus and urticaria; 13 patients developed transient thrombocytopenia less than 100,000/mm3. The maximum tolerated dose was not reached. All patients developed a monocytosis characterized by increased expression of the antigen HLA‐DR and decreased expression of CD14, a phenotype reported to represent a subpopulation of monocytes active in mediating antibody‐directed cellular cytotoxicity. Other biologic effects of treatment included marked but transient decreases in total cholesterol, low density lipoprotein, and high density lipoprotein. Three patients experienced tumor regression in breast, liver, and lymph node metastases and received a second course of therapy. Six of the 19 patients, one of whom received no further therapy, survived more than 2 years and 4 of these patients remain alive 24 to 37 months after treatment. Of the six patients with liver metastases, three (50%) survived more than 2.5 years and one remains alive at 37+ months. Conclusions. Combination therapy with R24 and M‐CSF resulted in both clinical and biologic effects that warrant further investigation of this combination. Copyright © 1995 American Cancer Society
Keywords:	adult; cancer survival; clinical article; controlled study; aged; middle aged; survival rate; clinical trial; liver neoplasms; lymph node metastasis; lymphatic metastasis; cancer immunotherapy; melanoma; metastasis; controlled clinical trial; gene expression; thrombocytopenia; antineoplastic activity; breast neoplasms; monoclonal antibody; pruritus; liver metastasis; cancer regression; antibodies, monoclonal; immunotherapy; hla dr antigen; hla-dr antigens; recombinant proteins; cholesterol; phase 1 clinical trial; antigens, cd; monocytes; infusions, intravenous; ganglioside gd3; cd14 antigen; urticaria; intravenous drug administration; colony stimulating factor 1; antigens, differentiation, myelomonocytic; antigens, cd14; monocytosis; gangliosides; ganglioside; recombinant colony stimulating factor 1; ganglioside antibody; macrophage colony-stimulating factor; humans; human; male; female; priority journal; article; monoclonal antibody r24; gd3; macrophage‐colony stimulating factor
Journal Title:	Cancer
Volume:	75
Issue:	9
ISSN:	0008-543X
Publisher:	Wiley Blackwell
Date Published:	1995-05-01
Start Page:	2251
End Page:	2257
Language:	English
DOI:	10.1002/1097-0142(19950501)75:9<2251::aid-cncr2820750910>3.0.co;2-f
PUBMED:	7536122
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028929089&doi=10.1002%2f1097-0142%2819950501%2975%3a9%3c2251%3a%3aAID-CNCR2820750910%3e3.0.CO%3b2-F&partnerID=40&md5=0fdb75f36e68d30b2f161386747aa044
Notes:	Article -- Export Date: 28 August 2018 -- Source: Scopus

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