Monoclonal antibody treatment directed to a cryptic epitope present within collagen (hu177) is as effective as ionizing radiation (rt) in inhibiting b16 melanoma growth: potential for combined treatment

Stella C. Lymbcris, Barry S. Rosenstein, Mary Louise Deitt, Peter C. Brooks, Silvia C. Formend'

Research output: Contribution to journalArticlepeer-review

Abstract

Proteolytic remodeling of the extracellular matrix (ECM) plays a critical role in regulating angiogenesis and tumor invasion. Monoclonal antibodies (Mabs) were developed that bind to distinct epitopes within collagen, selectively expressed during ECM remodeling. In several preclinical models, treatment with Mab directed to the HU177 epitope inhibits both angiogenesis and tumor growth in vivo. We previously reported that RT modulates the exposure of the HU126 cryptic epitope, but does not hinder the exposure of HU177(IJROBP 54(4):1194-1201,2002). We sought to examine the effect of Mab HU177 on tumor growth of B16 murine melanoma, and to compare its effect to a dose/fractionation regimen which is used in the clinic(Krishnan EC et al. Melanoma Res 1994; Ang KK et al, IJROBP1994). Materials and Methods: BALB/C mice were injected subcutaneously into the right flank on day 0 with 1X10 syngeneic B16 melanoma cells. On day 1, 38 mice were randomly assigned to the following four groups: no treatment, RT alone, Mab HU177, and nonspecific antibody. For both the Mab HU177 and for the non-specific antibody control groups, a dose of 100 ug was administered imraperitoneally starting on day 1 and continued every other day. Conversely, 60 Co RT was administered to the tumor 6 Gy X 5 (30 Gy total dose) starting on day 9, when the tumors in the no treatment group reached an average size of 450 mm 3. Results: At day 21, similar growth inhibition occurred in both the irradiated mice and those treated with Mab HU177 when compared to controls. Conclusion: These preliminary findings suggest that early, continued Mab HU177 treatment achieves growth inhibition comparable to that achieved by radiation. The combination of Mab HU177 and ionizing radiation is currently being explored.

Original languageEnglish
Pages (from-to)510
Number of pages1
JournalCancer journal (Sudbury, Mass.)
Volume9
Issue number6
DOIs
StatePublished - 1996
Externally publishedYes

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