CD22 is a suitable target molecule for detection and high-dose, myeloablative radioimmunotherapy with the monoclonal antibody LL2 in acute lymphatic leukaemia and Waldenstrom's macroglobulinaemia

T. M. Behr, E. Holler, S. Gratz, B. Wormann, R. M. Sharkey, R. M. Dunn, W. Hiddemann, H. J. Kolb, D. M. Goldenberg, W. Becker

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

CD22 is a 135-kD glycoprotein of the immunoglobulin superfamily which is expressed on most B lymphocytes. It has been used successfully as a target molecule for radioimmunodetection and therapy of B-cell non-Hodgkin's lymphoma with the monoclonal antibody CD22 (Mab), LL2. Since CD22 is highly expressed on blasts in acute lymphatic leukaemia of B-cell origin as well as on the malignant lymphocytes of macroglobulinaemia, we studied the potential of LL2 for the detection and therapy of these two haematological malignancies in two pilot cases. A 43-year-old male suffered from macroglobulinaemia, first diagnosed 4 years earlier. The IgM produced by the malignant clone cross-reacted with a ganglioside of peripheral neurons, causing severe and progressive sensomotor neuropathy. Several bone marrow biopsies as well as a splenectomy were not able to demonstrate the presence of a malignant clone which would be responsible for the IgM production. A localised tumour was suspected, but was not detected by any radiological procedure. Thus, the patient underwent radioimmunodetection (RAID) with 99mTc-LL2 Fab1 (LymphoScan(TM)). The second patient was a 28-year-old male who had common acute lymphatic leukaemia (c-ALL) for 8 years. He had failed 6 high-dose chemotherapy regimens with allogenic bone marrow or stem cell transplantations from his HLA-compatible brother. The patient had also failed two immunotherapeutic approaches with bispecific murine antibodies, which had caused high titres of HAMA. The patient was treated, with high-dose radioimmunotherapy with 131I-labelled humanised LL2 IgG in myeloablative intention with stem cell support. Although all diagnostic procedures had failed in the macroglobulinaemia patient, 99mTc-LL2 Fab1 showed excellent targeting of widespread parailiac, mediastinal, axillary and cervical lymph node involvement (all smaller than 1 cm in size) as well as a patchy uptake all over the patient's bone marrow as a sign of generalised tumour infiltration, precluding any localised treatment approach, such as external beam irradiation. The c-ALL patient underwent a diagnostic study with humanised LL2 (50 mg of protein, 8 mCi 131I) in order to assess tumour targeting and dosimetry, and was treated based on the result, with 258 mCi hLL2 at the same protein dose. Strong uptake occurred in the patient's bone marrow as well as in several extramedullary tumour sites (lymph nodes, spleen, muscular infiltration of the thigh). At a marrow dose of 30 Gy (whole-body 3.5 Gy, lung 12 Gy), the patient went into complete remission and bone marrow aplasia within two days. Reingraftment of the red marrow took place rapidly. The patient experienced a complete remission lasting for 7 weeks. Relapsed ALL and Waldenstrom's macroglobulinaemia seem to be suitable targets for a radioimmunotherapeutic approach with the anti-CD22 monoclonal antibody, LL2. Future studies will show whether high-dose RAIT with heterologous stem cell support may be able to induce longer-lasting remissions or even be curative in these haematologic malignancies.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalTumor Targeting
Volume3
Issue number1
StatePublished - 1998
Externally publishedYes

Keywords

  • Acute lymphatic leukaemia
  • CD22
  • High-dose myeloablative therapy
  • Lymphoma
  • Radioimmunotherapy
  • Waldenstrom's macroglobulinaemia

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