# PARANEOPLASTIC AUTOIMMUNITY--CALCIUM CHANNELS

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1993 · $269,621

## Abstract

The Lambert-Eaton myasthenic syndrome (LES) is an IgG-mediated
paraneoplastic autoimmune disorder of peripheral cholinergic synaptic
transmission that causes muscle weakness and autonomic dysfunction, and is
highly associated with small cell lung carcinoma (SCLC).  Autoimmunity in
LES appears to be the byproduct of a polyclonal IgG anti-tumor response
directed against neuronal-type voltage-gated Ca2+ channels (VGCC) expressed
in SCLC.  The anti-VGCC antibodies produced in patients with LES have
diverse specificities.  Some are reactive with (omega-CgTx)-binding
molecules (presumptive VGCC) expressed in human brain neurons and SCLC.
IgGs of this specificity are also found in some patients who have SCLC
without LES.  The long-term objectives of this research are to improve the
diagnosis and treatment of both LES and SCLC.

Tools for the proposed studies include:  frozen characterized sera from 200
LES patients: cryopreserved lymphocytes from 48 LES patients and numerous
control patients; fresh specimens of human brain; omega-CgTx-GVIA (a high
affinity ligand for some of the neuronal VGCC antigens that are
immunoprecipitable by LES IgG); defined SCLC lines binding components of
SCLC and neuronal membranes; CDNA probes and oligonucleotide primers and
probes encoding a prototypic rat neuronal omega-CgTx-binding (N-type) VGCC;
CDNA libraries (lambda gt11) made from RNAs of an omega-CgTx-binding SCLC
lineand from human brain neurons.

The Specific Aims are 1) to characterize and sequence the VGCC-like antigen
of SCLC to which LES IgG binds, and the neuronal VGCC antigens that are
targets for pathogenic IgG; ii) to use purified, recombinant and synthetic
peptide VGCC antigens, and monoclonal antibodies (Mabs), to define
immunologically the VGCC molecules (and epitopes) relevant to the
pathogenesis of LES; iii) to develop new animal models to investigate the
pathophysiological basis of neuromuscular and autonomic synaptic defects of
LES.

## Key facts

- **NIH application ID:** 3175169
- **Project number:** 5R01CA037343-08
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **SAM.gov UEI:** Y2K4F9RPRRG7
- **Principal Investigator:** VANDA A LENNON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $269,621
- **Award type:** 5
- **Project period:** 1984-03-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175169

## Citation

> US National Institutes of Health, RePORTER application 3175169, PARANEOPLASTIC AUTOIMMUNITY--CALCIUM CHANNELS (5R01CA037343-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175169. Licensed CC0.

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