TY - JOUR
T1 - Immunotherapy in a human ovarian cancer xenograft model with two bispecific monoclonal antibodies
T2 - OV-TL 3/CD3 and OC/TR
AU - Van Ravenswaay Claasen, Hedda H.
AU - Eggermont, Alexander M.M.
AU - Nooyen, Yvonne A.
AU - Warnaar, Sven O.
AU - Fleuren, Gert Jan
PY - 1994/2
Y1 - 1994/2
N2 - The bispecific antibodies (bs-mAbs) OV-TL 3/CD3 and OC/TR (MOv18/CD3) efficiently mediate ovarian tumor cell lysis by cytotoxic T cells and activated peripheral blood lymphocytes (PBL) in vitro. OV-TL 3/CD3 and OC/TR are reactive with tumor-associated antigens on ovarian carcinoma cells (OA3 and CA-MOv18, respectively), and CD3 on activated PBL, bridging both cells and simultaneously inducing activation of the effector cells. In a comparative study we investigated the therapeutic efficacy of OV-TL 3/CD3 and OC/TR by targeting activated PBL with the bs-mAbs against intraperitoneally growing NIH:OVAR-3 human ovarian carcinoma cells. As they have good tumor localization characteristics, HPLC-purified bispecific F(ab′)2 fragments were used to target highly active PHA and IL-2-stimulated PBL effector cells. The efficacy of OV-TL 3/CD3 was compared to OC/TR with respect to tumor- associated antigen (TAA) binding on NIH:OVCAR-3 ascites cells and NIH:OVCAR- 3 tumor cell lysis in vitro. In this report we show that ip ovarian cancer- bearing nude mice treated with IL-2 and activated PBL coated with bispecific F(ab′)2 had a significantly longer survival than the untreated mice. No significant difference in survival was found between the OC/TR or OV-TL 3/CD3 bispecific antibody, although MOv18 expression was higher on NIH:OVCAR-3 ascites cells and PBL targeted with OC/TR induced slightly higher tumor cell lysis in vitro. Thus, the therapeutic efficacy of these bs-mAbs in vivo could not be predicted by TAA expression or bs-mAbs-mediated tumor cell lysis in vitro.
AB - The bispecific antibodies (bs-mAbs) OV-TL 3/CD3 and OC/TR (MOv18/CD3) efficiently mediate ovarian tumor cell lysis by cytotoxic T cells and activated peripheral blood lymphocytes (PBL) in vitro. OV-TL 3/CD3 and OC/TR are reactive with tumor-associated antigens on ovarian carcinoma cells (OA3 and CA-MOv18, respectively), and CD3 on activated PBL, bridging both cells and simultaneously inducing activation of the effector cells. In a comparative study we investigated the therapeutic efficacy of OV-TL 3/CD3 and OC/TR by targeting activated PBL with the bs-mAbs against intraperitoneally growing NIH:OVAR-3 human ovarian carcinoma cells. As they have good tumor localization characteristics, HPLC-purified bispecific F(ab′)2 fragments were used to target highly active PHA and IL-2-stimulated PBL effector cells. The efficacy of OV-TL 3/CD3 was compared to OC/TR with respect to tumor- associated antigen (TAA) binding on NIH:OVCAR-3 ascites cells and NIH:OVCAR- 3 tumor cell lysis in vitro. In this report we show that ip ovarian cancer- bearing nude mice treated with IL-2 and activated PBL coated with bispecific F(ab′)2 had a significantly longer survival than the untreated mice. No significant difference in survival was found between the OC/TR or OV-TL 3/CD3 bispecific antibody, although MOv18 expression was higher on NIH:OVCAR-3 ascites cells and PBL targeted with OC/TR induced slightly higher tumor cell lysis in vitro. Thus, the therapeutic efficacy of these bs-mAbs in vivo could not be predicted by TAA expression or bs-mAbs-mediated tumor cell lysis in vitro.
UR - http://www.scopus.com/inward/record.url?scp=0028158120&partnerID=8YFLogxK
U2 - 10.1006/gyno.1994.1031
DO - 10.1006/gyno.1994.1031
M3 - Article
AN - SCOPUS:0028158120
SN - 0090-8258
VL - 52
SP - 199
EP - 206
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -