Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.
In a small number of patients, infusions of unirradiated donor leukocytes were an effective treatment for EBV-associated lymphoproliferative disease that arose after allogeneic bone marrow transplantation.
For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.
Data on the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children, [1][2][3][4] and in children with cancer specifically have been limited. Less than 1% of cases reported from China were in children younger than 10 years. 3 The MSK Kids pediatric program at Memorial Sloan Kettering Cancer Center (MSK) is one of the largest pediatric cancer programs in the US. Starting in mid-March, 2020, we instituted a screening and testing plan to mitigate risk associated with coronavirus disease 2019 (COVID-19).
Bone marrow transplantation (BMT) is the only known cure for the hematologic manifestations of Fanconi anemia (FA).Potential benefits of unrelated donor BMT for FA, however, have been severely limited by graft rejection and treatmentrelated mortality with resultant poor survival. Therefore, we evaluated the impact of potential prognostic factors on hematopoietic recovery, graft-versus-host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs 69%; P ؍ .02) and platelet (74% vs 23%; P < .001) recovery were higher after fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non-T-celldepleted grafts. The day-100 mortality rate was significantly higher after nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs 24%, respectively; P < .001). Corresponding 3-year adjusted overall survival rates were 13% versus 52% (P < .001). In addition, mortality was higher in recipients who were older (> 10 years), who were cytomegalovirus (
BACKGROUND. Adoptive transfer of donor-derived EBV-specific cytotoxic T-lymphocytes (EBV-CTLs) can eradicate EBVassociated lymphomas (EBV-PTLD) after transplantation of hematopoietic cell (HCT) or solid organ (SOT) but is unavailable for most patients.
METHODS.We developed a third-party, allogeneic, off-the-shelf bank of 330 GMP-grade EBV-CTL lines from specifically consented healthy HCT donors. We treated 46 recipients of HCT (n = 33) or SOT (n = 13) with established EBV-PTLD, who had failed rituximab therapy, with third-party EBV-CTLs. Treatment cycles consisted of 3 weekly infusions of EBV-CTLs and 3 weeks of observation.
RESULTS.EBV-CTLs did not induce significant toxicities. One patient developed grade I skin graft-versus-host disease. Complete remission (CR) or sustained partial remission (PR) was achieved in 68% of HCT recipients and 54% of SOT recipients. For patients who achieved CR/PR or stable disease after cycle 1, one year overall survival was 88.9% and 81.8%, respectively. In addition, 3 of 5 recipients with POD after a first cycle who received EBV-CTLs from a different donor achieved CR or durable PR (60%) and survived longer than 1 year. Maximal responses were achieved after a median of 2 cycles.
CONCLUSION.Third-party EBV-CTLs of defined HLA restriction provide safe, immediately accessible treatment for EBV-PTLD. Secondary treatment with EBV-CTLs restricted by a different HLA allele (switch therapy) can also induce remissions if initial EBV-CTLs are ineffective. These results suggest a promising potential therapy for patients with rituximab-refractory EBVassociated lymphoma after transplantation.Authorship note: SP and ED contributed equally to this work. Conflict of interest: ED and ROR had consultancy agreements with Atara Biotherapeutics. ED and ROR are inventors on technology referenced in this work (SK2013-71 [patient ID], Proprietary Cell Banks for Use in 3rd-Party EBV-Specific T Cell Therapy; and SK2018-122 [patient ID], Methods of Selecting T Cell Lines for Adoptive Cellular Therapy). SP is an inventor on technology referenced in this work (SK2013-71 and SK2018-122) and has waived rights to revenue generated from these inventions. Memorial Sloan Kettering Cancer Center (MSK), which owns the technology, has licensed this technology to Atara, and MSK has interests in Atara through this licensing arrangement.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.