State of the art and perspectives of chimeric antigen receptor T cells cell therapy for neuroblastoma.

Neuroblastoma (NB) is a solid, neuroendocrine pediatric solid tumor with divergent clinical behavior. Patients with high-risk diseases have poor prognoses despite complex multimodal therapy, which requires the search for new therapeutic approaches. Chimeric antigen receptor T cells (CAR-T) have led to dramatic improvements in the survival of cancer patients, most notably those with hematologic malignancies.

CAR-T Cell Therapy for Classical Hodgkin Lymphoma.

Classical Hodgkin lymphoma (cHL) is a malignancy characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells within a complex tumor microenvironment (TME). Despite advances in conventional therapies, a subset of cHL patients experience relapse or refractory disease, necessitating the exploration of novel treatment strategies. Chimeric antigen receptor T cell (CAR-T cell) therapy has emerged as a promising approach for the management of cHL, harnessing the power of genetically modified T cells to recognize and eliminate tumor cells.

Expression Pattern of Tumor-associated Antigens in Neuroblastoma: Association With Cytogenetic Features and Survival.

Background/aim: The prognosis of high-risk and relapsed neuroblastoma (NB) patients remains poor. The identification of tumor-associated markers is important for differential diagnosis, prognosis, and the development of targeted therapies. The aim of the study was to determine the expression profile of nine most common NB antigens and assess their association with clinicopathological characteristics and patient survival.

Design and Immunogenicity of SARS-CoV-2 DNA Vaccine Encoding RBD-PVXCP Fusion Protein.

The potential of immune-evasive mutation accumulation in the SARS-CoV-2 virus has led to its rapid spread, causing over 600 million confirmed cases and more than 6.5 million confirmed deaths. The huge demand for the rapid development and deployment of low-cost and effective vaccines against emerging variants has renewed interest in DNA vaccine technology.

Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library.

The COVID-19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 10 diverse phage display library in a manageable for a single person number of electroporation reactions.

Safety and Immunogenicity of Combined DNA-Polyethylenimine and Oral Bacterial Idiotypic Vaccine for Patients with B-Cell Non-Hodgkin Lymphoma: A Pilot Study.

We report, in brief, the results of a phase I, non-randomized study of idiotypic DNA vaccination in patients with B-cell non-Hodgkin's lymphoma (ISRCTN31090206). The DNA sequence of lymphoma-derived immunoglobulin variable regions was used as a tumor-specific antigen fused to the potato virus X coat protein. A conjugate of plasmid DNA with polyethylenimine was used for the intramuscular injections, followed by a boost with an oral live-attenuated vaccine carrying the same plasmid.

Aberrant IKZF1 gene as relapse predictor in standard-risk pediatric patients with B-cell precursor acute lymphoblastic leukaemia.

Introduction: Worldwide, the B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) treatment protocols are based on risk-adaptive therapy, that is on the search for biological markers for stratification by risk groups for optimal management. Depending on the treatment protocol, deletions and overexpression of non-functional IKZF1 isoforms act as relapse predictors in ALL. We investigated the IKZF1 gene aberrations as the substantive marker for predicting the development of relapse or adverse events when using risk stratification from ALL-MB-2002/2008 protocols.

Multi-antigen DNA vaccine delivered by polyethylenimine and Salmonella enterica in neuroblastoma mouse model.

Neuroblastoma is an example of a difficult-to-treat tumor with high incidence of relapse. DNA vaccination could be applied as a relapse prophylactic option for patients with high-risk neuroblastoma. Its efficacy depends directly on a target antigen of choice and a delivery method.

Autocrine-based selection of ligands for personalized CAR-T therapy of lymphoma.

We report the development of a novel platform to enhance the efficacy and safety of follicular lymphoma (FL) treatment. Since lymphoma is a clonal malignancy of a diversity system, every tumor has a different antibody on its cell surface. Combinatorial autocrine-based selection is used to rapidly identify specific ligands for these B cell receptors on the surface of FL tumor cells.

Changing of IKZF1 genotype during Philadelphia-negative precursor-B acute lymphoblastic leukemia progression: a short clinical report.

•The case demonstrated a rare event of clonal heterogeneity by IKZF1 gene status in BCRABL1- ALL.•IKZF1 deletions are secondary events in ALL caused by clonal evolution during the treatment.•It's prognostic significance could be more crucial in BCR-ABL- rather than in BCR-ABL + ALL.

Chimerism of allogeneic mesenchymal cells in bone marrow, liver, and spleen after mesenchymal stem cells infusion.

Although an infusion of culture-expanded MSCs is applied in clinic to improve results of HSCs transplantation and for a treatment of musculoskeletal disorders, homing, and engraftment potential of culture-expanded MSC in humans is still obscure. We report two female patients who received allogeneic BM transplantation as a treatment of hematological diseases and a transplantation of MSCs from third-party male donors. Both patients died within one yr of infectious complications.

Prognostic value of MRD-dynamics in childhood acute lymphoblastic leukemia treated according to the MB-2002/2008 protocols.

Detection of minimal residual disease (MRD) during the treatment of acute lymphoblastic leukemia (ALL) by RQ-PCR analysis of clonal Ig/TCR rearrangements is used for risk group stratification in European treatment protocols. In Belarus patients with childhood ALL are treated according to ALL-MB protocols, which do not use MRD-based risk stratification. To evaluate the prognostic significance of MRD for ALL-MB-2002/2008 protocols, MRD was quantified by RQ-PCR in 68 ALL patients at four time points: on day 15, on day 36, before and after maintenance therapy (MT).

Relative expression of different Ikaros isoforms in childhood acute leukemia.

Ikaros is a zinc-finger transcriptional factor playing an essential role in lymphoid lineage commitment and differentiation. Animal models and analysis of human Ikaros in leukemic cells demonstrate deregulation of Ikaros expression. Short isoforms with a truncated DNA-binding domain suppress functions of Ikaros in a dominant-negative manner.

Immunophenotypically heterogeneous acute T-lymphoblastic leukemia has invariable immunogenotype: analysis of two cases.

Two patients with acute T-lymphoblastic leukemia showed heterogeneous expression of some immunophenotypic cell markers. Cell sorting was used to separate two CD34/CD117/TCRgammadelta and CD34/CD117/TCRgammadelta cell populations. The sorted TCRgammadelta population had more cells in S phase than the TCRgammadelta population.

The incidence of T-cell receptor gene rearrangements in childhood B-lineage acute lymphoblastic leukemia is related to immunophenotype and fusion oncogene expression.

Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangement is conventionally used for assessment of lymphoid malignant cells. TCR genes rearrangements were reported to occur at high frequency in B-lineage acute lymphoblastic leukemia (ALL). Therefore, we have analyzed 83 children with acute B-lineage ALL (67 de novo patients and 19 relapses) by PCR analysis for clonal IgH, incomplete TCRD (Vdelta2-Ddelta3 and Ddelta2-Ddelta3) and TCRG rearrangements.