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Neuroantibodies: molecular cloning of a monoclonal antibody against substance P for expression in the central nervous system.

ABSTRACT: We present a strategy to study functional and/or developmental processes occurring in the nervous system, as well as in other systems, of mice. This strategy is based on the local expression of specific monoclonal antibodies (mAbs) by cells of the nervous system. As an application of this strategy, we report the cloning of the anti-substance P rat mAb NC1/34HL. Functional substance P-binding antibodies were reconstituted from the cloned variable domains by using vectors for expression in myeloma cells. With these and other vectors a general system for the cloning and expression of mAbs under a series of promoters (of the rat VGF8a gene, the neurofilament light-chain gene, and the methallothionein gene) has been created. The activity of these plasmids was confirmed by expressing the recombinant NC1/34HL mAb in GH3 pituitary cells, PC12 pheochromocytoma cells, and COS cells. DNA from the described constructs can be used to target the expression of the NC1/34HL mAb to the central nervous system of transgenic mice. This procedure will allow us to perturb substance P activity in a controlled way in order to dissect its multiple roles.

SUBMITTER: Piccioli P

PROVIDER: S-EPMC51927 | biostudies-other | 1991 Jul

REPOSITORIES: biostudies-other

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Neuroantibodies: molecular cloning of a monoclonal antibody against substance P for expression in the central nervous system.

Piccioli P P Ruberti F F Biocca S S Di Luzio A A Werge T M TM Bradbury A A Cattaneo A A

Proceedings of the National Academy of Sciences of the United States of America 19910701 13

We present a strategy to study functional and/or developmental processes occurring in the nervous system, as well as in other systems, of mice. This strategy is based on the local expression of specific monoclonal antibodies (mAbs) by cells of the nervous system. As an application of this strategy, we report the cloning of the anti-substance P rat mAb NC1/34HL. Functional substance P-binding antibodies were reconstituted from the cloned variable domains by using vectors for expression in myeloma ...[more]

PMID: 1712102

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Project description:CD20-negative diffuse large B-cell lymphoma (DLBCL) is a rare type of lymphoproliferative disorder characterized by a high degree of aggressiveness, a tendency for extranodal invasion and chemotherapeutic resistance. CD20-negative DLBCL originating from the nervous system is rarer. In primary central nervous system lymphoma (PCNSL), >90% of cases are histologically classified as DLBCL. The present study reports the case of a 65-year-old female with CD20-negative PCNSL, whose primary clinical symptom was a persistent headache. Serum tests for human immunodeficiency virus, Epstein-Barr virus-DNA, human herpesvirus 8, hepatitis B and hepatitis C were negative. Cranial magnetic resonance imaging suggested multiple intracranial occupancies. The neoplastic cells were found to be positive for CD19, CD79α, Bcl-2 (~92%) and c-Myc (~50%), while showing negative results for CD20, CD138, programmed cell death protein 1 (PD-1) and programmed cell death receptor 1 ligand 1 (PD-L1). The Ki-67 proliferation index was >80%. In the tumor microenvironment, <10% of the tumor-associated macrophages expressed PD-L1. The number of PD-1-positive tumor-infiltrating lymphocytes was 30-40 cells according to high-power field microscopy. The patient's disease progressed during methotrexate-based treatment, leading to a change in the treatment regimen to the Bruton tyrosine kinase inhibitor, zanubrutinib, combined with the anti-PD-1 monoclonal antibody tislelizumab. After two courses of the combined treatment, the patient achieved complete remission (CR) and continued to receive consolidation treatment. In the 20 months of follow-up since CR was achieved, the patient's general condition was good and the disease was in continuous remission. The present case report and literature review show that a combination of drugs targeting different mechanisms may be used to treat PCNSL to prolong patient survival time. The mechanism of the enhanced efficacy of a combination of the two drugs may be related to the enhancement of antitumor T-cell immune responses and reversal of T-cell immune metabolic dysfunctions by the inhibition of glycolysis.

Dataset Information

Neuroantibodies: molecular cloning of a monoclonal antibody against substance P for expression in the central nervous system.

Publications

Neuroantibodies: molecular cloning of a monoclonal antibody against substance P for expression in the central nervous system.

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