A Bright Horizon: Immunotherapy for Pediatric T-Cell Malignancies

Round 1

Reviewer 1 Report

The article represents a synthetic and comprehensible review of the current level of immunotherapy development in T cell malignancies

The authors have written a well-systematized presentation of the immunotherapy methods addressed to T-cell neoplasias in children, in which the potential targets, potential hurdles, methods to overcome the obstacles and the ongoing studies are described.

I  recommend the publication of the article

Author Response

Thank you very much!

Reviewer 2 Report

I enjoyed reading this review article.  I have a couple of suggestions that are obviously not compulsory for it's publication.

1st I'd suggest in the section regarding TCR knockouts to include the work published in Nature regarding TRAC locus replacement with CAR.

"Eyquem, J., Mansilla-Soto, J., Giavridis, T. et al. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543, 113–117 (2017). https://doi.org/10.1038/nature21405"

2nd when discussing strategies to limit fratricide a recent publication in Nature comms,  showed that Dasatinib (a potent src kinase inhibitor) was able to allow for the expansion of anti-GRP78 CAR T cells during their manufacture whilst eliminating fratricide associated with GRP78 expression on the T cells themselves.  This could be a useful strategy to employ during the manufacture of T-ALL CARs.

Hebbar, N., Epperly, R., Vaidya, A. et al. CAR T cells redirected to cell surface GRP78 display robust anti-acute myeloid leukemia activity and do not target hematopoietic progenitor cells. Nat Commun 13, 587 (2022). https://doi.org/10.1038/s41467-022-28243-6

Other minor points:

The section 3.2.1 starting "Pan and Colleagues" I feel reads a little clunky and a rephrase may help to maintain clarity

The term "Piggybacking" may not be easily translatable to a wider scientific audience beyond those that are native English speakers and I'd suggest changing this.

There are two sections pertaining to CAR T cell Therapy, would it be better to combine these?  It may disrupt the flow and I leave this up to your discretion.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf