- Paper Report
- Open Access
Enhanced activity of anti-Lewisyhumanised 3S193 when combined with Taxol
- Richard de Boer1
© Current Science Ltd 2000
- Published: 1 December 2000
- Breast cancer
- Ley antigen
- murine model
Monoclonal antibody (mAB) therapy is a potential new treatment option that selectively targets tumours and produces a therapeutic effect via the delivery of radiation or other toxins directly to tumour cells, or by producing an intrinsic immune inflammatory response. The Lewisy antigen (Ley) is a difucosylated oligosaccharide expressed on the surface of up to 60% of breast cancer cells, whilst rarely expressed on normal tissues. The humanised murine antibody, hu35193 has been shown to have high specificity for Ley.
To examine the antitumour effect of 131I-labelled hu3S193 in an MCF-7 xenografted BALB/c nude mouse breast cancer model compared with that of placebo and radiolabelled huA33 control antibody. To examine the synergy between radioimmunotherapy and chemotherapy using a combination of 131I-labelled hu3S193 and Taxol.
mABs were produced using standard hybridoma techniques and then humanised. MCF-7 cells were used as the tumour target, and SW1222, a LeY negative colonic cancer cell line was used as control. Tumour cells were injected into the left inguinal mammary line of 5-6 week old BALB/c nude mice and supported by slow release oestrogen pellets. Antibodies were radiolabelled the day of injection. In the first part of the study, antibody with escalating doses of iodine (50, 100, 200 and 300 μCi) was injected 22 days after tumour inoculation and effect on tumour volume measured. In the second part of the study, the determined dose of iodine-labelled antibody was injected with or without intraperitoneal Taxol. This component of the study incorporated nine different treatment groups (some acting as controls).
The maximum tolerated dose of 131I-labelled antibody was 200 μCi/mouse. At this dose level three out of six mice receiving 131I-hu3S193 had a partial tumour response and two out of six had a minor response. There were no responses in the comparable 131I-huA33 control treatment arm. A significant dose-response relationship was seen for 131I-hu3S193. Unlabelled antibody had little impact upon tumour growth. In the combination part of the study, the combination of 600 μg Taxol and 100 μCi 131I-hu3S193 produced partial tumour inhibition in 80% of mice, while no significant responses were seen with either treatment modality alone or the combination of Taxol and 131I-huA33.
These results confirm that specifically targeted radiolabelled antibody can effectively slow tumour growth in a murine model. In addition, combining the antibody with a chemotherapeutic agent increased the antitumour efficacy. Thus, the study indicates a potential therapeutic role for radiolabelled hu3S193 in the management of breast cancer, either as a single agent or in combination with Taxol, and warrants further investigation of this new agent.