# AUTOIMMUNE PARANEOPLASTIC SYNDROMES

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1987 · $33,828

## Abstract

The Lambert-Eaton myasthenic syndrome (LES) is a disease of neuromuscular
transmission in which there is a deficient quantal release of acetylcholine
(ACh) in response to a nerve impulse.  Its etiology remains unknown.
Striking features of this disease include a high incidence of bronchogenic
carcinoma (plus or minus 65% of patients), usually of the small cell (oat
cell) type (SCC), and a high prevalence of autoantibodies (e.g., to
specific thyroid and stomach constituents). Passive transfer of plasma
immunoglobulins from patients to mice causes a defect in neuromuscular
transmission similar to that of LES.

Our hypothesis is that failure of neuromuscular transmission in the LES
results from an autoimmune response against cholinergic neurons or related
structures, which may be initiated by an antitumor immune response directed
against a neuron-related differentation antigen of SCC.  We plan to study
SCC immunologically to determine whether or not the tumors or their
products can express antigens related to cholinergic neurons.  Sera from
LES patients with and without carcinoma will be tested for reactivity with
SCC, cholinergic neurons, and other neural substrates.  Cholinergic nerve
terminals from the electric organ of Torpedo californica will be
investigated as another potential source of antigen relevant to LES.
Monoclonal antibodies raised against SCC and cholinergic neuron components
will be used both to identify and purify the antigens of relevance.

This project's goal is to determine the nature of the primary autoimmune
abnormality in LES.  A related goal is to establish an animal model for LES
that:  (1) will facilitate detailed analysis of the mechanisms responsible
for the failure of release of ACh quanta in LES; (2) may yield a serologic
test for diagnosis of LES and/or small cell carcinoma; and (3) will allow
evaluation of new modes of therapy for LES and/or small cell carcinoma.
(IB)

## Key facts

- **NIH application ID:** 3175163
- **Project number:** 3R01CA037343-03S1
- **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:** 1987
- **Award amount:** $33,828
- **Award type:** 3
- **Project period:** 1984-03-01 → 1988-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175163

## Citation

> US National Institutes of Health, RePORTER application 3175163, AUTOIMMUNE PARANEOPLASTIC SYNDROMES (3R01CA037343-03S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175163. Licensed CC0.

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