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Among pts with CLL/SLL, the median number of prior lines of therapy was 4 (range, 2-18), all pts received prior BTKi therapy, 27 (47%) received prior BTKi and BCL2i therapy, and 36 (63%) had C481S-mutated BTK. B Background: b Bruton tyrosine kinase inhibitors (BTKis) are standard of care for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but resistance can develop, most commonly because of BTK mutations. AbbVie, AstraZeneca, BeiGene, Century Therapeutics, Genentech, Genmab, Hutchison MediPharma, Iksuda Therapeutics, InnoCare Pharma, Janssen, Kite Pharma, MorphoSys, Myeloid Therapeutics, Novartis, Nurix Therapeutics, Pharmacyclics, Roche, Secura Bio, Servier Pharmaceuticals, Takeda, TG Therapeutics, Verastem, Vincerx Pharma, Xencor Research funding: Research Grants: All payments made to Sarah Cannon Research Institute, not to the physician. [Extracted from the article]

LISOCABTAGENE MARALEUCEL (LISO-CEL) IN R/R CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL): PRIMARY ANALYSIS OF TRANSCEND CLL 004 B Introduction: b Achieving durable CR with current treatment is uncommon in patients (pts) with R/R CLL/SLL that progressed on BTKi and failed venetoclax (ven)-based treatment. Keyword: cellular therapies B Conflicts of interests pertinent to the abstract b B T. Siddiqi b Consultant or advisory role: Astra Zeneca, BMS, Celgene, Kite pharma, Beigene, Abbvie Research funding: Astra Zeneca, BMS, Celgene, Oncternal, Ascentage pharma, Kite pharma, TG therapeutics, Pharmacyclics, Juno therapeutics Other remuneration: Speaker's Bureau: Astra Zeneca, BMS, Beigene B D. G. Maloney b Consultant or advisory role: A2 Biotherapeutics, Member of the Scientific Advisory Board GRAPH Navan Technologies, Member of the Scientific Advisory Board GRAPH Chimeric Therapeutics, Member of the Scientific Advisory Board GRAPH Genentech, Member and Chair of the Lymphoma Steering Committee GRAPH BMS, Member of the JCAR017 EAP-001 Safety Review Committee GRAPH BMS, Member, CLL Strategic Council GRAPH ImmPACT Bio, Member, Clinical Advisory Board, CD19/CD20 bi-specific CAR-T Cell Therapy Program GRAPH Gilead Sciences, Member, Scientific Review Committee, Research Scholars Program in Hematologic Malignancies GRAPH Interius. [Extracted from the article]

Consensus Panel 5 (CP5) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11; held in October 2022) was tasked with reviewing the current data on the coronavirus disease-2019 (COVID-19) prophylaxis and management in patients with Waldenstrom's Macroglobulinemia (WM). The key recommendations from IWWM-11 CP5 included the following: Booster vaccines for SARS-CoV-2 should be recommended to all patients with WM. Variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4.5 strain, are important as novel mutants emerge and become dominant in the community. A temporary interruption in Bruton's Tyrosine Kinase-inhibitor (BTKi) or chemoimmunotherapy before vaccination might be considered. Patients under treatment with rituximab or BTK-inhibitors have lower antibody responses against SARS-CoV-2; thus, they should continue to follow preventive measures, including mask wearing and avoiding crowded places. Patients with WM are candidates for preexposure prophylaxis, if available and relevant to the dominant SARS-CoV-2 strains in a specific area. Oral antivirals should be offered to all symptomatic WM patients with mild to moderate COVID-19 regardless of vaccination, disease status or treatment, as soon as possible after the positive test and within 5 days of COVID-19-related symptom onset. Coadministration of ibrutinib or venetoclax with ritonavir should be avoided. In these patients, remdesivir offers an effective alternative. Patients with asymptomatic or oligosymptomatic COVID-19 should not interrupt treatment with a BTK inhibitor. Infection prophylaxis is essential in patients with WM and include general preventive measures, prophylaxis with antivirals and vaccination against common pathogens including SARS-CoV-2, influenza, and S. pneumoniae., (Copyright © 2023 Elsevier Inc. All rights reserved.)

HIV-1 SF13 emerged in a patient with immunity to HIV-1 SF2. This study determined the effect of antibodies raised to HIV-1 SF2 on the replication of the later variant. Antisera in rats were raised previously to a complete set of overlapping, synthetic 15mer peptides following the sequence of HIV-1 SF2 gp120. These sera have now been used in neutralization and enhancement assays against viruses derived from molecular clones of both variants. The sets of peptides inducing neutralizing antibodies to the two variants overlap. Antibodies to the third variable region of HIV-1 SF2 only neutralize the homologous virus whereas those to the second and fourth variable regions neutralize both variants. In contrast, the sets of major epitopes involved in enhancement do not overlap. Epitopes for both variants form two clusters when superimposed on the conformation of the conserved regions. To determine if antibodies with the potential to enhance or neutralize HIV-1 SF2 change over time in infected individuals sera from chimpanzees were used because no material was still available from the original patient. Antibodies to HIV-1 SF2 neutralizing epitopes and HIV-1 SF13 enhancing epitopes were present in the circulation of chimpanzees infected with HIV-1 SF2. Once antibodies to the neutralizing epitopes were induced they persisted whereas antibodies to the enhancing epitopes varied with time after infection. Conditions may therefore exist within individual hosts where not only neutralizing but also enhancing antibodies have the potential to contribute to the selection pressure operating on the circulating population of polymorphic variants., (Copyright 2001 Wiley-Liss, Inc.)

We have developed a unique multiple step procedure to inactivate human immunodeficiency virus chemically with a very high safety margin while retaining antigenically active structural virion proteins, including gp120, in the final immunogen. The whole virus preparation (1-10 micrograms per dose) was highly immunogenic in a variety of small mammals and induced antibodies that recognized homologous and heterologous strains of HIV-1. Sera from immunized animals bound to peptides representing the entire sequence of the external glycoprotein gp120. Neutralizing antibodies active against the homologous immunizing strain and against heterologous HIV-1 strains were also elicited. Sera with virus neutralizing activity did not bind to MHC class I proteins derived from the human cell line used to grow the virus.

An insertion sequence, IS1081, in the genome of Mycobacterium bovis has been identified and sequenced. It is 1324 bp long with 15 bp inverted repeat ends and contains a large ORF. There are six copies of IS1081 in the genome of M. bovis and the element is also present in Mycobacterium tuberculosis. IS1081 is not closely related to other DNA elements described in actinomycetes but its putative transposase bears some resemblance to that of IS256 from Staphylococcus aureus. IS1081 may be useful for genetic manipulations and for developing a diagnostic test for bovine tuberculosis based on the polymerase chain reaction.