24

breast, gastric, and colonic adenocarcinomas

and some tumors of neuroectodermal origin.

Group 2 antibodies, which are both of IgG3

subclass imnxnoprecipitate a nonglycosylated

MSr) 24,000 polypeptide. Group 3 antibodies

(PF3/A, an IgGl; PF3/B, and IgGM; and PF3/C,

an IgG2a) react additionally with certain

other tumors, as well as with normal adult

and fetal epidermis. Group 4 antibodies

(PF4/A, an IgG2a; and PF4/B, an IgGl) are

less specific than those of the preceding

groups, as they react with some normal

tissues, including pancreatic islets and

pneumocytes, as well as with a variety of

adenocarcinomas and tumors of neuroectoder-

mal origin. PF4/A and PF4/B im-

munoprecipitate (M(r) I00,000 and 95,000

glycoproteins, respectively.

Cytotoxic Murine Monoclonal Antibody LAM8

With Specificity for Human Small Cell Car-

cinoma of the Lung.

Stahel, R.A., O'Hara, C.J., Mabry, M. et al.

Division of Oncology, Department of

Medicine, University Hospital of Zurich, CH-

8091 Zurich, Switzerland. Cancer Res. 46:

2077-2084, 1986.

The reactivity of the murine im-

munoglobulin monoclonal antibody LAM8

directed against a membrane antigen of ~m~n

small cell carcinoma (SCC) of the lung was

investigated on human cell lines and

tissues. Indirect immmofluorescence stain-

ing, radioimmunoassays, and cytotoxicity as-

says showed LAM8 antibody to selectively

react with SCC but not with non-SCC lung

cancer cell lines and extrapulmonary tumor

cell lines. Unlike other SCC antibodies, in-

cluding those we have previously described,

highly preferential reactivity with SCC

tissues was also demonstrated by im-

munoperoxidase staining of deparaffinized

formalin-fixed tissue sections. Membrane and

cytoplasmic staining was seen in of 9 of 12

SCC tissues. No significant staining was

seen in non-SCC lung cancer and a wide range

of other tumors, including mesothelioma and

bronchial carcinoids. Significant LAM8 reac-

tivity was also absent in normal tissues of

all major organs. Few tumors and epithelial

tissues, including bronchial epithelium had

rare LAM8 positive cells which were always

less than 2% of the entire cell population.

In vitro treatment with antibody and ~,nnn

complement was highly cytotoxic to SCC

cells, but had no effect on bone marrow

progenitor cells. Immunoblotting of membrane

extracts separated on sodium dodecyl

sulfate-polyacrylamide gels showed the LAM8

antigen to have a band of an approximate

molecular weight of 135,000 and a cluster of

bands with approximate molecular weights of

90,000. This reactivity was lost after in-

cubation of the extracts with periodate.

LAM8 antibody shows a highly preferential

reactivity with SCC cell lines and formalin-

fixed paraffin-embedded SCC tissues and is

selectively cytotoxic to cells expressing

LAM8 antigen.

Anti-Neurofilament Antibodies in the Sera of

Patients with Small Cell Carcinoma of the

Lung and With Visual Paraneop lastic

Syndrome.

Kornguth, S.E., Kalinke, T., Grunwald, G.B.

et al. Department of Neurology, University

of Wisconsin, Madison, WI, U.S.A. Cancer

Res. 46: 2588-2595, 1986.

The sera of patients with small cell

caricnoma of the lung (SCCL) and an as-

sociated visual paraneoplastic syndrome

(VPNS) have higher titer ~oglobulins

that react with retinal ganglion cells and

with cloned lines of the SCCL. The im-

munoglobulins in the sera of two patients

with SCCL and VPNS reacted with at least one

common antigen shared by neural cells and

cloned lines of the SCCL. The molecular

weights of the predominant neural and tumor

antigens were 205,000, 145,000, 65,000, and

20,000-24,000 as determined by Western

blots. Three of the antigens from neural

tissue copurify and comigrate

electrophoretically with neurofilament

proteins. Polyclonal antibodies prepared

against authentic neurofilament proteins

react with antigens having molecular weights

identical to those of proteins t_hat react

with immunoglobulins form the SCCL-VPNS

patients. Polyclonal antibodies that were

prepared against isolated retinal ganglion

cells and that were shown previously to

cause the inmn/noablation of the ganglion

cells in vivo reacted most intensely with

the M(r) 205,000 antigen and weakly with the

M(r) 145,000 and M(r) 70,000 antigens.

Treatment of the Western blots with alkaline

phosphatase from Escherichia coli did not

affect the immunoreactivity between the im-

munoglobulins and the purified neurofilament

proteins. It is proposed t_hat the im-

munoglobulins in the sera of patients with

SCCL-VPNS may be involved etiologically in

the development of the VPNS.