Antitumor effects of nonconjugated murine Lym-2 and human-mouse chimeric CLL-1 monoclonal antibodies against various human lymphoma cell lines in vitro and in vivo

Satoshi Funakoshi, Akio Hirano, Margaret Beckwith, Osamu Asai, Gitte Jorgensen, Zhi Gang Tian, Jason L. Hornick, Peisheng Hu, Leslie A. Khawli, Alan L. Epstein, Dan L. Longo, William J Murphy

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Lym-2 is a murine monoclonal antibody (MoAb) directed towards e human class II molecule variant reactive with both normal and neoplastic human 8 lymphocytes. Previous studies have shown that signals transmitted by class II molecules that stimulate normal lymphocytes can be inhibitory for B-cell lymphoma growth by signaling activation-induced cell death. Therefore, we sought to evaluate the effects of non-conjugated murine Lym-2 and a human- mouse chimeric Lym-2 (chCLL-1; with murine variable regions and human constant regions) MoAb on the growth of various human lymphomas by using both in vitro and in vivo assays. Cell lines derived from Burkitt's lymphomas, diffuse large cell B-cell lymphomas, anaplastic large-cell lymphomas, and Epstein-Bart virus-induced B-cell lymphomas were incubated with Lym-2 or chCLL-1 in vitro, and effects on proliferation were determined by [3H]- thymidine incorporation. The effects of Lym-2 in vitro were also compared with those of Lym-1, which is a similar MoAb that has been evaluated clinically. After immobilization, which enhances crosslinking of the MoAbs, both Lym-2 and chCLL-1 were capable of directly inhibiting the growth of various lymphoma lines in vitro. These human lymphomas were then transferred into mice with severe combined immunodeficiency to evaluate the efficacy of these MoAbs in vivo. Treatment with either murine Lym-2 or the chimeric chCLL-1 were significantly effective in improving the survival of tumor- bearing mice. These results indicate that stimulation by nonconjugated chCLL- 1 may offer a biological approach to the treatment of various human lymphomas.

Original languageEnglish (US)
Pages (from-to)3160-3166
Number of pages7
JournalBlood
Volume90
Issue number8
StatePublished - Oct 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Antitumor effects of nonconjugated murine Lym-2 and human-mouse chimeric CLL-1 monoclonal antibodies against various human lymphoma cell lines in vitro and in vivo'. Together they form a unique fingerprint.

  • Cite this

    Funakoshi, S., Hirano, A., Beckwith, M., Asai, O., Jorgensen, G., Tian, Z. G., Hornick, J. L., Hu, P., Khawli, L. A., Epstein, A. L., Longo, D. L., & Murphy, W. J. (1997). Antitumor effects of nonconjugated murine Lym-2 and human-mouse chimeric CLL-1 monoclonal antibodies against various human lymphoma cell lines in vitro and in vivo. Blood, 90(8), 3160-3166.