Single-dose versus fractionated radioimmunotherapy of human colon carcinoma xenografts using 131I-labeled multivalent CC49 single-chain Fvs1

A. Goel, Samuel C. Augustine, J. Baranowska-Kortylewicz, D. Colcher, B. J M Booth, G. Pavlinkova, M. Tempero, S. K. Batra

Research output: Contribution to journalArticle

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Abstract

The prospects of radiolabeled antibodies in cancer detection and therapy remain promising. However, efforts to achieve cures, especially of solid tumors, with the systemic administration of radiolabeled monoclonal antibodies (MAbs) have met with limited success. Using genetic engineering techniques, MAbs have been tailored to improve the therapeutic index (tumor:normal tissue ratio) in clinical radioimmunotherapy. In the present study, we investigated the potential of tetravalent {[sc(Fv)2]2} and divalent [sc(FV)2] single chain Fvs of MAb CC49 for therapy in athymic mice bearing s.c. LS-174T human colon carcinoma xenografts. Mice received 1000 μCi of 131I-labeled [sc(Fv)2]2 or 131I-labeled sc(Fv)2, either as a single injection on day 6 or as four injections (250 μCi each) on days 6, 7, 8, and 9; the day of tumor implantation was taken as day 0. The median survival for the control group was 26 days. Comparisons of single and fractionated therapeutic regimens showed median survival as 32 (P <0.001) and 53 days (P <0.0001), respectively for [sc(Fv)2]2 and 26 (P > 0.5) and 38 days (P <0.0001), respectively for sc(Fv)2 when compared with the control groups. The time for the quadrupling of tumor volume for single and fractionated therapeutic treatments were: 9.0 ± 0.8 and 21.1 ± 2.9 days respectively for sc(Fv)2; 16.6 ± 1.9 and 32.9 ± 2.7 days respectively for [sc(Fv)2]2; and 8.3 ± 0.7 and 8.4 ± 0.6 days respectively for the control group. No 131I-labeled systemic toxicity was observed in any treatment groups. The results show that radioimmunotherapy delivery for sc(Fv)2 and [sc(Fv)2]2 in a fractionated schedule clearly presented a therapeutic advantage over single administration. The treatment group receiving tetravalent scFv showed a statistically significant prolonged survival with both single and fractionated administrations suggesting a promising prospect of this reagent for cancer therapy and diagnosis in MAb-based radiopharmaceuticals.

Original languageEnglish
Pages (from-to)175-184
Number of pages10
JournalClinical Cancer Research
Volume7
Issue number1
StatePublished - 2001
Externally publishedYes

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Radioimmunotherapy
Heterografts
Colon
Carcinoma
Therapeutics
Neoplasms
Control Groups
Survival
Monoclonal Antibodies
Genetic Techniques
Injections
Genetic Engineering
Radiopharmaceuticals
Tumor Burden
Nude Mice
Appointments and Schedules

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Goel, A., Augustine, S. C., Baranowska-Kortylewicz, J., Colcher, D., Booth, B. J. M., Pavlinkova, G., ... Batra, S. K. (2001). Single-dose versus fractionated radioimmunotherapy of human colon carcinoma xenografts using 131I-labeled multivalent CC49 single-chain Fvs1. Clinical Cancer Research, 7(1), 175-184.

Single-dose versus fractionated radioimmunotherapy of human colon carcinoma xenografts using 131I-labeled multivalent CC49 single-chain Fvs1. / Goel, A.; Augustine, Samuel C.; Baranowska-Kortylewicz, J.; Colcher, D.; Booth, B. J M; Pavlinkova, G.; Tempero, M.; Batra, S. K.

In: Clinical Cancer Research, Vol. 7, No. 1, 2001, p. 175-184.

Research output: Contribution to journalArticle

Goel, A, Augustine, SC, Baranowska-Kortylewicz, J, Colcher, D, Booth, BJM, Pavlinkova, G, Tempero, M & Batra, SK 2001, 'Single-dose versus fractionated radioimmunotherapy of human colon carcinoma xenografts using 131I-labeled multivalent CC49 single-chain Fvs1', Clinical Cancer Research, vol. 7, no. 1, pp. 175-184.
Goel, A. ; Augustine, Samuel C. ; Baranowska-Kortylewicz, J. ; Colcher, D. ; Booth, B. J M ; Pavlinkova, G. ; Tempero, M. ; Batra, S. K. / Single-dose versus fractionated radioimmunotherapy of human colon carcinoma xenografts using 131I-labeled multivalent CC49 single-chain Fvs1. In: Clinical Cancer Research. 2001 ; Vol. 7, No. 1. pp. 175-184.
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