PONE-D-23-41952Control of acute myeloid leukemia and generation of immune memory in vivo using AMV564, a bivalent bispecific CD33 x CD3 T cell engagerPLOS ONE

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PLOS ONE

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: In this manuscript Eissenberg et al describe bispecific T engager AVM564 as a potential therapeutic for AML. This is a well written manuscript that describes additional preclinical work with a novel agent with potential for translation to the clinic and intriguing data suggesting potential lasting immunologic effects. In this resubmission the authors address the prior reviewers critiques adequately and clearly describe the limitations around pursuing additional experiments for this publication.

Critiques are primarily limited to grammatical edits and suggestions to improve clarity for the reader.

Minor Comments:

Spelling error throughout: Albumin rather than Albumen

Would move the FAB subtype comment to the Cells subheading

Would clearly state the limitation that no control bispecific or activated T cells were utilized in the animal work.

Line 353 extra space in initially

Reviewer #2: The manuscript by Eissenberg et al reports the preclinical efficacy of bispecific antibodies targeting CD33. That antibody treatment can impart tumor immunity demonstrated by protection against rechallenge is an interesting observation. In addition to using AML cell lines, data in a primary AML sample with 2% T cells are presented.

Major

No survival data is reported for the primary patient sample study in mice. It would be interesting to see if rechallenge with primary sample in this model is ineffective and does not lead to leukemia.

Did not find Figs. 4F and 4G. Although BLI signal was high in these mice, the authors claim that the mice did not die from tumor, referring to Fig. 4G. This is confusing.

The following minor point should be addressed.

Consider revising “induces protective immunity in an immunodeficient model’ in the abstract, as it is confusing.

Redirect CD3+ cells to CD3 epsilon? First sentence in introduction, please revise.

What would be the source of allogeneic T cells in a patient? Will immunity be restricted to patients who have undergone HCT?

Please correct typo – albumin instead of albumen

Can the authors comment on why 4 doses were used in Fig 2, while 5 doses were used in other experiments

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Reviewer #1: No

Reviewer #2: Yes: Sonali Barwe

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Control of acute myeloid leukemia and generation of immune memory in vivo using AMV564, a bivalent bispecific CD33 x CD3 T cell engager

PONE-D-23-41952R1

Dear Dr. Patel

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Anilkumar Gopalakrishnapillai

Academic Editor

PLOS ONE

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