Radioimmunotherapy with Tenarad, a 131I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma

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• 作者：Luigi Aloj (5)
  Laura D’Ambrosio (1)
  Michela Aurilio (1)
  Anna Morisco (1)
  Ferdinando Frigeri (2)
  Corradina Caraco-/a> (1)
  Francesca Di Gennaro (1)
  Gaetana Capobianco (2)
  Leonardo Giovannoni (3)
  Hans D. Menssen (3)
  Dario Neri (4)
  Antonio Pinto (2)
  Secondo Lastoria (1)
  
• 关键词：Hodgkin's lymphoma ; Radioimmunotherapy ; Dosimetry ; 131I ; Tenascin ; C
• 刊名：European Journal of Nuclear Medicine and Molecular Imaging
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：41
• 期：5
• 页码：867-877
• 全文大小：2,165 KB
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• 作者单位：Luigi Aloj (5)
  Laura D’Ambrosio (1)
  Michela Aurilio (1)
  Anna Morisco (1)
  Ferdinando Frigeri (2)
  Corradina Caraco-/a> (1)
  Francesca Di Gennaro (1)
  Gaetana Capobianco (2)
  Leonardo Giovannoni (3)
  Hans D. Menssen (3)
  Dario Neri (4)
  Antonio Pinto (2)
  Secondo Lastoria (1)
  
  5. Struttura Complessa di Medicina Nucleare, Istituto Nazionale Tumori “Fondazione G. Pascale-- IRCCS, Via M. Semmola, 80131, Napoli, Italy
  1. Struttura Complessa Medicina Nucleare, Istituto Nazionale Tumori “Fondazione G. Pascale-- IRCCS, Napoli, Italy
  2. Struttura Complessa di Ematologia Oncologica, Istituto Nazionale Tumori “Fondazione G. Pascale-- IRCCS, Napoli, Italy
  3. Philogen, SpA, Siena, Italy
  4. Institute of Pharmaceutical Sciences, ETH, Zurich, Switzerland
  
• ISSN：1619-7089

文摘

Purpose The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the extracellular matrix of tumours and on newly formed blood vessels and is thus a valuable target for radionuclide therapy. Tenarad is a fully human miniantibody or small immunoprotein (SIP, molecular weight 80 kDa) labelled with 131I that is derived from a TC-A1-binding antibody. Previous phase I/II studies with a similar compound (131I-L19SIP) used for radioimmunotherapy (RIT) have shown preliminary efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad was administered to patients with recurrent Hodgkin's lymphoma (HL) refractory to conventional treatments. Methods Eight patients (four men, four women; age range 19?–?1) were enrolled between April 2010 and March 2011. All patients had received a median of three previous lines of chemotherapy (range three to six) and seven had also undergone autologous stem cell transplantation (ASCT) or bone marrow transplantation. In addition, seven patients received external beam radiation. All patients had nodal disease, constitutional B symptoms and some showed extranodal disease in skeletal bone (four patients), lung (three), liver (two) and spleen (one). Baseline assessments included whole-body FDG PET with contrast-enhanced CT and diagnostic Tenarad planar and SPECT studies. Patients were considered eligible to receive a therapeutic dose of Tenarad (2.05?GBq/m2) if tumour uptake was more than four times higher than that of muscle. Results All patients were eligible and received the therapeutic dose of Tenarad. Only one patient developed grade 4 thrombocytopenia and leucocytopenia, requiring hospitalization and therapeutic intervention. All other patients had haematological toxicity of grade 3 or lower, which resolved spontaneously. At the first response assessment (4?–??weeks after therapy), one patient showed a complete response, one showed a partial response (PR) and five had disease stabilization (SD). Five patients were given up to three repeated Tenarad treatments. One patient showed SD which then improved to a PR, three showed clinical benefit while maintaining SD and one patient showed disease progression. Conclusion Tenarad RIT is effective in chemorefractory HL and resulted in objective responses or clinical benefit in the majority of patients. Toxicity was acceptable despite the high load of prior treatments, previous ASCT and multiple Tenarad administrations. Further studies are planned to define the most effective schedule for this type of RIT in HL patients.