Conference Coverage

Abs from transplanted AML patients enhance GvL effect in vitro


 

Mette Hazenberg, MD, PhD

NEW YORK—Investigators have found that B cells may play a role in stimulating graft-versus-leukemia (GvL) responses in patients with acute myeloid leukemia (AML) who have undergone allogeneic hematopoietic stem cell transplant (HSCT).

The team created B cell lines from these patients, isolated AML-specific antibodies, and found that these antibodies can induce the death of AML cells through oncosis.

Oncosis is a non-apoptotic type of cell death that involves swelling and coagulation of the cytoplasm.

Mette Hazenberg, MD, PhD, from the Academic Medical Center in Amsterdam, The Netherlands, reported these findings at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference as poster B052.

The investigators cloned B cells from 3 high-risk AML patients who had a strong GvL response after HSCT.

The team transduced memory B cells from the patients’ peripheral blood using BCL-6 and BCL-xL. They then screened the B cells for those that produced antibodies that bound specifically to surface antigens on AML cell lines and blasts.

Six of the 15 AML antibodies retrieved from the patients bound specifically to snRNp200. In normal cells, snRNp200 is in the nucleus, but, in AML, it is exposed on the cell membrane.

The investigators then confirmed this by ELISA.

They found 7 of the 15 AML antibodies directly lysed AML blasts without the addition of effector cells or complement. Time-lapse images showed that cell death by the AML antibodies occurred rapidly, within minutes after incubation.

“The leukemia blasts popped like balloons,” Dr Hazenberg said.

The investigators confirmed that the antibodies induced cell death by oncosis and that oncosis occurred independently of temperature. The antibodies were cytotoxic at 4°C and 37°C.

Cytotoxicity of the antibodies could be blocked by the membrane stabilizer cytochalasin D but not by apoptosis inhibitors.

The team concluded that a potent GvL response could be mediated by these antibodies against tumor-associated antigens on AML cells.

Dr Hazenberg’s hope is that, at some point, these antibodies can be combined with chemotherapy—as is rituximab—so patients won’t need to undergo transplant.

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