Abstract
An immunoconjugate (PF1/D-DAVLBHYD), made with the squamous carcinoma reactive monoclonal antibody PF1/D and a derivative of vinblastine, DAVLBHYD, was shown to suppress established T222 human tumor nude mouse xenografts using a multidose protocol. Treatments of xenograft-bearing mice with free drug, free antibody, or a mixture of the two, were unsuccessful at achieving suppression without associated toxicity, using otherwise identical protocols. A Vinca conjugate with a related squamous carcinoma reactive monoclonal antibody, PF1/B, was shown to have similar tumor suppressive activity. In a dual immunoconjugate therapy protocol, PF1/D-DAVLBHYD and PF1/B-DAVLBHYD had additive antitumor effects which were consistent with their complementary tumor reactivity.
Keywords: Nude Mouse, Antitumor Effect, Vinblastine, Free Drug, Suppressive Activity
Abbreviations
- PBS
0.01 M sodium phosphate, pH 7.4 plus 0.15 M NaCl
- DAVLBHYD
4-desacetylvinblastine-3-carboxhydrazide
- DMEM
Dulbecco's modified Eagle's medium
- FCS
fetal calf serum
References
- 1.Ackers GK. Analytical gel chromatography of proteins. Adv Protein Chem. 1970;24:343. doi: 10.1016/s0065-3233(08)60245-4. [DOI] [PubMed] [Google Scholar]
- 2.Borowitz MJ, Croker BP, Metzgar RS. Lymphoblastic lymphoma with the phenotype of common acute lymphoblastic leukemia. Am J Clin Pathol. 1983;79(3):387. doi: 10.1093/ajcp/79.3.387. [DOI] [PubMed] [Google Scholar]
- 3.Bumol TF, Simmonds RG, Boder GB, Cullinan G, Marder P, Apelgren L. Immunotherapy of human solid tumor xenografts with Vinca alkaloid-monoclonal conjugates. J Cell Biochem. 1985;9:54. [Google Scholar]
- 4.Conrad RA, Cullinan GJ, Gerzon K, Poore GA. Structure-activity relationships of dimeric Catharanthus alkaloids. 2. Experimental antitumor activities of N-substituted desacetylvinblastine amide (vindesine) sulfates. J Med Chem. 1979;22:391. doi: 10.1021/jm00190a008. [DOI] [PubMed] [Google Scholar]
- 5.Fernsten P, Pekny KW, Reisfeld RA, Walker LE. Antigens associated with human squamous cell lung carcinoma defined by murine monoclonal antibodies. Cancer Res. 1986;46:2970. [PubMed] [Google Scholar]
- 6.Geran RI, Greenberg NH, MacDonald MM, Schumacher AM, Abbot BJ. Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother Rep. 1972;3(2):1. [Google Scholar]
- 7.Ghose T, Blair AH, Vaughan K, Kulkarni P. Antibody directed drug targeting in cancer therapy. In: Goldberg EP, editor. Targeted drugs. New York: J. Wiley & Sons; 1983. p. 1. [Google Scholar]
- 8.Johnson DA, Laguzza BC. Antitumor xenograft activity with a conjugate of a Vinca derivative and the squamous carcinoma-reactive monoclonal antibody PF1/D. Cancer Res. 1987;47:3118. [PubMed] [Google Scholar]
- 9.Masui H, Kawamono T, Sato JD, Wolf B, Sato G, Mendelsohn J. Growth inhibition of human tumor cells in athymic mice by anti epidermal growth factor receptor antibodies. Cancer Res. 1984;44(3):1002. [PubMed] [Google Scholar]
- 10.Reisfeld RA, Cherish DA. Human tumor associated antigens for monoclonal antibody mediated cancer therapy. Cancer Surv. 1985;4:271. [PubMed] [Google Scholar]
- 11.Rowland GF, Axton CA, Baldwin RW, Brown JP, Embleton F, Gore MJ, Hellstrom I, Hellstrom KE, Jacobs E, Marsden CH, Pimm MV, Simmonds RG, Smith W. Antitumor properties of vindesine-monoclonal antibody conjugates. Cancer Immunol Immunother. 1985;19:1. doi: 10.1007/BF00199304. [DOI] [PMC free article] [PubMed] [Google Scholar]