False-Positive Human Immunodeficiency Virus Type 1 Nucleic Acid Amplification Testing in Chimeric Antigen Receptor T Cell Therapy.

We describe three clinical scenarios in which CAR T- cell immunotherapy interfered with HIV-1 testing including: (1) routine infectious disease screening prior to stem cell transplantation in a 16-year-old female with B-cell acute lymphoblastic leukemia, status post CAR T- cell treatment (2) routine infectious disease screening prior to 2nd CAR T- cell collection in a 65-year-old male with diffuse large B-cell lymphoma who failed initial CAR T- cell treatment and (3) routine infectious risk assessment following an occupational health exposure from a 58 -year-old male with multiple myeloma, status post CAR T- cell treatment. In each case, patients initially tested negative by the fourth generation HIV-1 screening enzyme immunoassay (targeting p24 antigen and anti-HIV-1 antibodies), but positive by the Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1-1 Test, v2.0 (targeting gag and LTR). These samples were subsequently retested negative using the Abbott Realtime m2000 HIV-1-1 assay which targets the integrase gene. These results indicated that cross reactions between lentiviral vectors and LTR genomes targeted in the HIV-1-1 NAAT caused the HIV-1 NAAT false positive results. PMID: 31694968 [PubMed - as supplied by publisher]
Source: Clinical Lymphoma and Myeloma - Category: Cancer & Oncology Authors: Tags: J Clin Microbiol Source Type: research

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Chimeric antigen receptor (CAR)-T cell therapy is a new and powerful class of cancer immunotherapy [1,2]. Clinical trials of CAR-T cell therapy targeting the B-cell marker CD19 have shown promising results for the treatment of hematologic malignancies, including acute lymphoblastic leukemia (ALL) [3 –7], chronic lymphocytic leukemia (CLL) [8,9], and non-Hodgkin lymphoma (NHL) [10,11]. CAR-T cell therapy targeting B-cell maturation antigen (BCMA) has also been demonstrated to be effective for treating multiple myeloma (MM) [12–15].
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
This study aimed to analyze the role of postoperative treatment for BC in the development of subsequent HM. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident primary breast cancer between 2007 and 2015, who underwent surgery as first-line treatment for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Analyses were censored at HM o...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionThe use of a pediatric-inspired protocol for high-risk AYA ALL patients was effective and well tolerated with improvement in OS and DFS compared with historical data using adult protocols in such populations.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Chimeric antigen receptor (CAR)-modified T cell therapy is a rapidly emerging immunotherapeutic approach that is revolutionizing cancer treatment. The impressive clinical results obtained with CAR-T cell therapy in patients with acute lymphoblastic leukemia and lymphoma have fueled the development of CAR-T cells targeting other malignancies, including multiple myeloma (MM). The field of CAR-T cell therapy for MM is still in its infancy, but remains promising. To date, most studies have been performed with B cell maturation antigen (BCMA)-targeted CARs, for which high response rates have been obtained in early-phase clinica...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionThe use of pediatric-inspired protocol for high risk AYA ALL was effective and well tolerated with improvement in OS and DFS compared to historical data using adult protocols in such population
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Treatment of acute lymphoblastic leukemia (ALL) in adolescent and young adult (AYA) patients using traditional adult chemotherapy protocols give low overall survival (OS) rates. The purpose of this prospective study was to assess efficacy and tolerability of treatment of AYA patients using a pediatric-inspired protocol modified from the Children ’s Cancer Group 1900 protocol for newly diagnosed high-risk Philadelphia chromosome-negative ALL patients. Forty patients with a median age of 18 years (range, 14-34 years) were enrolled in the study. Treatment was effective with a complete remission rate after induction of 9...
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, CAR-T treatment combined with intratumoral delivery of poly I:C resulted in synergistic antitumor activity. We thus provide a rationale to translate this immunotherapeutic strategy to solid tumors. Introduction Adoptive T cell immunotherapy has been demonstrated to be a new way to fight malignancies. In particular, T lymphocytes engineered to express chimeric antigen receptor (CAR) have shown great promise in treating hematological malignancies (1). CD19-targeted CAR-T cells have been approved by FDA to treat relapsed B cell acute lymphoblastic leukemia (B-ALL) and Diffuse Large B-cell lymphoma (DLBC...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions The major challenges in the development of adoptive cell therapy for T cell tumors, as mentioned above, remain fratricide, T cell aplasia and the potential for leukemic transduction or poor T cell function if used in the autologous setting. Approaches to overcome fratricide include the genetic modification and deletion of the T cell antigen in the case of long-term CAR-T cell persistence or regulated CAR-T expression. To ensure restoration of T cell immunity, transient CAR expression can be achieved incorporation of a CAR suicide gene, transient CAR expression using mRNA electroporation, or short-lived NK cell...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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