This project is designed to explore the diagnostic and therapeutic potential of a panel of monoclonal antibodies (MoAbs) that react with SCCL-associated or specific cell surface antigens. The majority of the MoAbs were prepared in this laboratory during the first years of this on-going study (now in its 4th year) and in addition, we have acquired two SCCL-reactive MoAbs, TFS-2 and TFS- 4 that augment our ability to carry out the studies we propose. In particular, we will undertake a prospective evaluation of SCCL tumor immunophenotyping for the purpose of establishing meaningful clinical correlations. All patients with lung cancer seen at the DHMC will have their tumor cells examined by immunohistochemistry for the expression of antigens defined by a battery of MoAbs. The tumor registry of DHMC will collect the clinical data thus permitting data analyses and correlations. A second project will be the development of a sensitive test for the detection of small numbers of SCCL cells in other cell populations, such as bone marrow. This will involve the use of multiparameter flow cytometry to measure simultaneously DNA content and surface expression of SCCL 175. This technique will be used to establish the incidence of bone marrow metastases and to monitor the efficacy of SCCL purging of bone marrow for autologous bone marrow transplantation (ABMT). Another project will examine the potential of MoAbs to remove SCCL cells from bone marrow using immunomagnetic beads. We will explore the use of several MoAbs conjugated to magnetic microspheres for their abilities, alone and in combination, to prepare marrow from SCCL patients tumor-free for ABMT. Finally, we will prepare hetero-antibodies (HA) of anti-SCCL MoAbs and MoAbs to cytotoxic effector cells. These HA will be examined for their abilities to mediate SCCL killing. We expect these pre-clinical studies to lead immediately to clinical applications for the diagnosis and treatment of patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA037868-05
Application #
3175751
Study Section
Experimental Immunology Study Section (EI)
Project Start
1985-09-30
Project End
1994-05-31
Budget Start
1989-06-01
Budget End
1990-05-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Dartmouth College
Department
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Vredenburgh, J J; Simpson, W; Memoli, V A et al. (1991) Reactivity of anti-CD15 monoclonal antibody PM-81 with breast cancer and elimination of breast cancer cells from human bone marrow by PM-81 and immunomagnetic beads. Cancer Res 51:2451-5
Ball, E D; Powers, F J; Vredenburgh, J J et al. (1991) Purging of small cell lung cancer cells from bone marrow using immunomagnetic beads and a flow-through device. Bone Marrow Transplant 8:35-40
Ball, E D; Vredenburgh, J J; Mills, L E et al. (1990) Autologous bone marrow transplantation for acute myeloid leukemia following in vitro treatment with neuraminidase and monoclonal antibodies. Bone Marrow Transplant 6:277-80
Vredenburgh, J J; Ball, E D (1990) Elimination of small cell carcinoma of the lung from human bone marrow by monoclonal antibodies and immunomagnetic beads. Cancer Res 50:7216-20
Memoli, V A; Jordan, A G; Ball, E D (1988) A novel monoclonal antibody, SCCL 175, with specificity for small cell neuroendocrine carcinoma of the lung. Cancer Res 48:7319-22
Ball, E D; Keefe, K A; Colby, E (1987) Expression of antigens associated with small cell carcinoma of the lung on hematopoietic progenitor cells. Cancer Res 47:6556-9
Ball, E D; Nichols, K E; Pettengill, O S et al. (1986) Lysis of small cell carcinoma of the lung tumor cell lines by gamma interferon-activated allogeneic peripheral blood mononuclear cells: abrogation of killing by pretreatment of tumor cells with gamma interferon. Cancer Immunol Immunother 22:211-6
Ball, E D; Sorenson, G D; Pettengill, O S (1986) Expression of myeloid and major histocompatibility antigens on small cell carcinoma of the lung cell lines analyzed by cytofluorography: modulation by gamma-interferon. Cancer Res 46:2335-9