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Multicenter Study
. 2010 Aug;150(3):352-8.
doi: 10.1111/j.1365-2141.2010.08251.x. Epub 2010 Jun 7.

Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia

Francis Mussai  1 , Dario Campana, Deepa Bhojwani, Maryalice Stetler-Stevenson, Seth M Steinberg, Alan S Wayne, Ira Pastan
Affiliations
Multicenter Study

Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia

Francis Mussai et al. Br J Haematol. 2010 Aug.

Abstract

Acute lymphoblastic leukaemia (ALL) remains the most frequent cause of cancer-related mortality in paediatrics and outcome is poor for patients who have high-risk ALL or relapse. HA22 (CAT-8015) is an immunotoxin composed of an anti-CD22 variable fragment linked to a 38 kDa truncated protein derived from Pseudomonas exotoxin A. Using a bone marrow mesenchymal cell culture assay to support ALL cell viability, we investigated the in vitro cytotoxicity of HA22 against ALL blasts from newly diagnosed (n = 13) and relapsed patients (n = 22). There was interpatient variability in sensitivity to HA22. Twenty-four of 35 patient samples tested were sensitive (median 50% lethal concentration 3 ng/ml, range 1-80 ng/ml). Blasts from the other 11 patients were not killed by 500 ng/ml HA22. The median 50% lethal concentration was 20 ng/ml for all patients. There was no significant difference in HA22 sensitivity between diagnosis and relapse samples but peripheral blood ALL blasts were more sensitive to HA22 than those from bone marrow (P = 0.008). Thus, HA22, at concentrations achievable in patients, is highly cytotoxic to B-lineage ALL cells. These results provide a strong rationale for clinical testing of this agent in children with drug-resistant ALL and offers the potential to reduce morbidities of treatment while improving outcome.

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Conflict of interest statement

Disclosure of potential conflict of interest

Ira Pastan is a co-inventor on patents assigned to the NIH for the investigational product used in this research.

Figures

Fig 1.
Fig 1.
No difference in cytotoxicity of HA22 against paediatric ALL cells from relapsed and newly diagnosed patients. (A) Scatter plot of the percentage of viable ALL cells remaining after 72 h incubation with 500 ng/ml HA22 for samples. (B) Scatter plot of the 50% lethal concentration (LC50) results for HA22.
Fig 2.
Fig 2.
CD22 expression in patients is varied and is weakly correlated with HA22 cytotoxicity.
Fig 3.
Fig 3.
Cytotoxicity of HA22, but not dexamethasone, appears to be greater against blasts from peripheral blood compared to those from bone marrow.
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