Proposal for translational analysis and development of clinical radiolabeled immunoglobulin therapy

Huibert M. Vriesendorp, Syed M. Quadri, Kurt Jaeckle, Ralph S. Freedman, D. M. Cromeens

Research output: Contribution to journalArticle

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Abstract

Background and purpose: Radiolabeled immunoglobulin therapy (RIT) can be a selective, effective, low-toxicity outpatient cancer therapy. A consensus on the best approach for the preclinical and clinical development of RIT reagents needs to be developed. We report the M.D. Anderson Cancer Center prior experience in translating RIT from laboratory to clinic for the treatment of Hodgkin's disease and propose a flow diagram for the development of RIT for other malignancies. Material and methods: Three different animal models are described: nude mice bearing human tumor xenografts, normal beagle dogs, and normal rhesus monkeys. We produced and purified antibodies and prepared chelate-immunoconjugates reactive with six different human tumor-associated antigens. The Igs used were derived from rabbits, mice, and humans (human-derived RIT reagents being less immunogenic in human patients). Eighty patients with refractory Hodgkin's disease were treated with radiolabeled antiferritin. Results: We recommend a two-injection scheme using, (1) an indium-111-labeled radioimmunoconjugate for diagnosis, pharmacokinetic studies, and dosimetry, and (2) a yttrium-90-labeled radioimmunoconjugate for therapy. The animal models provide useful data on tumor targeting, radiotoxicology, and undesirable biodistributions. A 70% response rate is obtained in patients with advanced recurrent Hodgkin's disease. More extensive preclinical testing allows for safer and more effective clinical RIT studies. Conclusions: We recommend, (1) preclinical optimization of chelation chemistry, Ig size, Ig origin, route of administration, and fractionation, (2) new clinical Phase I-III studies more appropriate for RIT development than the classical Phase I-III studies used for the development of chemotherapeutic agents, and (3) more extensive preclinical testing of RIT reagents.

Original languageEnglish (US)
Pages (from-to)151-161
Number of pages11
JournalRadiotherapy and Oncology
Volume41
Issue number2
DOIs
StatePublished - Nov 1 1996

Fingerprint

Passive Immunization
Immunoconjugates
Hodgkin Disease
Neoplasms
Animal Models
Yttrium
Indium
Neoplasm Antigens
Macaca mulatta
Heterografts
Nude Mice
Outpatients
Therapeutics
Pharmacokinetics
Dogs
Rabbits
Injections
Antibodies

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Vriesendorp, Huibert M. ; Quadri, Syed M. ; Jaeckle, Kurt ; Freedman, Ralph S. ; Cromeens, D. M. / Proposal for translational analysis and development of clinical radiolabeled immunoglobulin therapy. In: Radiotherapy and Oncology. 1996 ; Vol. 41, No. 2. pp. 151-161.
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abstract = "Background and purpose: Radiolabeled immunoglobulin therapy (RIT) can be a selective, effective, low-toxicity outpatient cancer therapy. A consensus on the best approach for the preclinical and clinical development of RIT reagents needs to be developed. We report the M.D. Anderson Cancer Center prior experience in translating RIT from laboratory to clinic for the treatment of Hodgkin's disease and propose a flow diagram for the development of RIT for other malignancies. Material and methods: Three different animal models are described: nude mice bearing human tumor xenografts, normal beagle dogs, and normal rhesus monkeys. We produced and purified antibodies and prepared chelate-immunoconjugates reactive with six different human tumor-associated antigens. The Igs used were derived from rabbits, mice, and humans (human-derived RIT reagents being less immunogenic in human patients). Eighty patients with refractory Hodgkin's disease were treated with radiolabeled antiferritin. Results: We recommend a two-injection scheme using, (1) an indium-111-labeled radioimmunoconjugate for diagnosis, pharmacokinetic studies, and dosimetry, and (2) a yttrium-90-labeled radioimmunoconjugate for therapy. The animal models provide useful data on tumor targeting, radiotoxicology, and undesirable biodistributions. A 70{\%} response rate is obtained in patients with advanced recurrent Hodgkin's disease. More extensive preclinical testing allows for safer and more effective clinical RIT studies. Conclusions: We recommend, (1) preclinical optimization of chelation chemistry, Ig size, Ig origin, route of administration, and fractionation, (2) new clinical Phase I-III studies more appropriate for RIT development than the classical Phase I-III studies used for the development of chemotherapeutic agents, and (3) more extensive preclinical testing of RIT reagents.",
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Proposal for translational analysis and development of clinical radiolabeled immunoglobulin therapy. / Vriesendorp, Huibert M.; Quadri, Syed M.; Jaeckle, Kurt; Freedman, Ralph S.; Cromeens, D. M.

In: Radiotherapy and Oncology, Vol. 41, No. 2, 01.11.1996, p. 151-161.

Research output: Contribution to journalArticle

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T1 - Proposal for translational analysis and development of clinical radiolabeled immunoglobulin therapy

AU - Vriesendorp, Huibert M.

AU - Quadri, Syed M.

AU - Jaeckle, Kurt

AU - Freedman, Ralph S.

AU - Cromeens, D. M.

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N2 - Background and purpose: Radiolabeled immunoglobulin therapy (RIT) can be a selective, effective, low-toxicity outpatient cancer therapy. A consensus on the best approach for the preclinical and clinical development of RIT reagents needs to be developed. We report the M.D. Anderson Cancer Center prior experience in translating RIT from laboratory to clinic for the treatment of Hodgkin's disease and propose a flow diagram for the development of RIT for other malignancies. Material and methods: Three different animal models are described: nude mice bearing human tumor xenografts, normal beagle dogs, and normal rhesus monkeys. We produced and purified antibodies and prepared chelate-immunoconjugates reactive with six different human tumor-associated antigens. The Igs used were derived from rabbits, mice, and humans (human-derived RIT reagents being less immunogenic in human patients). Eighty patients with refractory Hodgkin's disease were treated with radiolabeled antiferritin. Results: We recommend a two-injection scheme using, (1) an indium-111-labeled radioimmunoconjugate for diagnosis, pharmacokinetic studies, and dosimetry, and (2) a yttrium-90-labeled radioimmunoconjugate for therapy. The animal models provide useful data on tumor targeting, radiotoxicology, and undesirable biodistributions. A 70% response rate is obtained in patients with advanced recurrent Hodgkin's disease. More extensive preclinical testing allows for safer and more effective clinical RIT studies. Conclusions: We recommend, (1) preclinical optimization of chelation chemistry, Ig size, Ig origin, route of administration, and fractionation, (2) new clinical Phase I-III studies more appropriate for RIT development than the classical Phase I-III studies used for the development of chemotherapeutic agents, and (3) more extensive preclinical testing of RIT reagents.

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