Professional Documents
Culture Documents
5689 Full
5689 Full
1989|
Downloaded from cancerres.aacrjournals.org on June 28, 2017. 1989 American Association for Cancer Research.
HUMAN IgGj MAb DIRECTED TO AN UNBRANCHED REPEATING TYPE 2 CHAIN
AcnLcft) (16), H2 (VI2FucnLc6) (17), H, (VI2FuclV>-Fuca2Gal/34Glc- tions that had been incubated with SP2 culture supernatant served as a
NAcnLc6) (17), and G, (VI'NeuAcIV('Fuc2Gal/i4GlcNAcnLc(,) (18) negative control. Avidin and biotin were purchased from Vector (Vec
were prepared from human O erythrocytes. nLc8 was purified from tastatin, Burlingame. CA).
rabbit muscle (19), and G,0 (VI1NeuAcIV<'Fuca2Gal/i4GlcNAcnLc6) Fluorocytometry was performed using fluorescein isothiocyanate-
(19-21) was from human placenta. PG, nLc,,, and Gg., were prepared conjugated anti-human IgG (goat, Tago, Burlingame, CA) in PICS
by mild acid hydrolysis of SPG, sialosylnorhexaosylCer, and CM, Profile (Coulter). The control value was that without the primary
ganglioside, respectively. Lactoisooctaosylceramide (I antigen) was pre antibody.
pared from G10. Antibody-dependent Cytotoxicity Assay and Complement-dependent
Assessment of the Reactivity of M \l> with Various Glycolipids by Cytotoxicity Assay. ADCC was studied by a 4-h chromium release assay
Solid-Phase Enzymoimmunoassay. The enzymoimmunoassay was per as previously described (27). Peripheral blood lymphocytes from a
formed using various glycolipid antigens that were immobilized at the healthy donor were separated by Ficoll Paque (Pharmacia, Piscataway,
bottom of 96-well culture plates (Costar, Cambridge, MA) as described NJ). The effectortarget cell ratios were 100:1, 50:1, and 25:1. HL-60
previously (22). Briefly, the plate was blocked with PBS containing 5% cells were labeled for 2 h with 100 ^Ci of MCr in RPMI 1640 medium
BSA for 2 h and incubated for l h with medium containing the MAb. supplemented with 3% FCS at 37Cin a CO2 incubator and washed
After washing five times with PBS/0.5% BSA, the plate was incubated three times and resuspended in medium. MCr-labeled HL-60 cells were
for I h with medium containing peroxidase-conjugated goat anti-human placed in 96-well round-bottom plates (Costar, Cambridge, MA) at a
IgG (7 chain specific) (Cappel. Malvern, PA). density of 5 x 10' cells/well, and various numbers of effector cells (5 x
10', 2.5 x 10', and 1.25 x IO5) were added per well, followed by
Preparation of Neutral Glycolipid Fraction from Various Kinds of
Tissues. Cancer tissues were removed surgically from patients with addition of various concentrations of MH21-134 (50, 5, 0.5, and 0.05
various kinds of carcinomas. Neutral glycolipids of these cancer tissues Mg/ml) in RPMI 1640 supplemented with 20% FCS. For direct effector
were prepared as follows. Glycolipids were extracted from cancer tissues cell lysis and total release by addition of 2% Triton X-100, medium
with isopropanol-hexane-water (55:20:25) (23) and partitioned accord alone was added to some wells. The plate was then centrifuged at 400
ing to Folch-Pi (24). The glycolipids in the upper layer fraction of the x g for 3 min and incubated for 16 h at 37Cin a CO: incubator. After
Folch's partition were subjected to DEAE-Sephadex A-25 (Pharmacia, 2% Triton X-100 was added for total release wells, the plate was
Uppsala, Sweden) column chromatography (25). After the neutral centrifuged at 700 x g for 5 min, and radioactivity was measured in an
glycolipids were eluted with CMW (30:60:8), gangliosides were eluted 80-fil aliquot of each supernatant using a gamma counter. Spontaneous
with chloroform-methanol-0.8 N sodium acetate (30:60:8). The neutral MCr release was determined in wells that contained labeled HL-60 cells
glycolipid mixture in the former fraction was used for TLC immuno- and effector cells. There were three replicates per group. The % cytolysis
staining without further purification. was calculated as follows:
TLC Immunostaining. TLC immunostaining was performed with the
Experimental release - spontaneous release
neutral glycolipids extracted from cancer tissues according to the % Cytolysis = x 100
method originally introduced by Magnani et al. (26), with modifications Total release - spontaneous release
(22). Briefly, glycolipids were developed on a Baker high-performance
thin-layer chromatography plate (Si-HPF plate, 7011-3; Baker, Phil- Complement-dependent Cytotoxicity was studied in HL-60 cells using
rabbit complement with MCr release assay. The difference between
lipsburg, NJ) with a solvent system of CMW (50:40:10). The plate was
air dried and blocked with PBS/5% BSA for 2 h and exposed overnight control (without complement) at 4 and 24 h was determined.
to the culture fluid containing respective MAbs (about 5 ^g/ml). After
washing five times with PBS/0.5% BSA. the plate was exposed for l h
to the solution of rabbit anti-human IgG (y chain specific, ICN Im- RESULTS
munobiologicals. Lisle, IL). After five washings with PBS/0.5% BSA, Specificity of MAb MH21-134. Among various hybridomas
the plate was exposed to the PBS containing I25l-Protein A for l h and
secreting MAbs reacting with PC-9 and KATO III, stable clones
washed 10 times with PBS. The plate was then air dried and subjected
to autoradiography. that could be propagated in nu/nu mice were selected. One of
Immunohistochemical Techniques and Fluorocytometric Analysis. The these seven MAbs detected neutral glycolipids of KATO III,
avidin-biotin complex technique for the immunohistochemical study of for it did not react with KATO III cells treated with HIOj but
various kinds of cancers was performed as described below. Briefly, did react with those treated with sialidase. When the specificity
tumor sections of 4-/jm thickness were freed of paraffin by soaking in of this MAb, MH21-134, was tested by solid-phase enzymoim
xylene and dehydrated in graded ethanol. The endogenous peroxidase munoassay using various standard glycolipids as antigens, a
activity was blocked by treating the sections with 0.3% hydrogen significant reaction was obtained with nLc6 and nLcx, and no
peroxide for 20 min. After washing for 5 min in 50 mM Tris buffer, pH reactivity was observed with LacCer, Gbj (CTH), Ggj (asialo
7.4, the sections were incubated for 2 h at room temperature with PBS/ CM,), Lc4 (PG), Gb4 (globoside), SPG, Forssman, sialosyl-
5% BSA and then exposed overnight to the biotinylated MAb of the
MH21-134 hybridoma. MH21-134 hybridoma was propagated in nu/ nLc,,, H2, Hj, G,o, and lactoisooctaosylceramide (I antigen)
nu mice as ascites, and the antibody was purified from the ascites using (Fig. 1, a and b). This specificity was confirmed by TLC
Sepharose 4B affinity gels to human IgG (Cappel, Malvern, PA). One
immunostaining, in which MH21-134 reacted only with nLc,,
mg MH21-134 antibody/ml 0.1 M sodium acetate buffer (pH 5.5) was and nLcx (Fig. 2). These results indicate that the epitope of
oxidized at 0Cfor 20 min with 10 m.Msodium periodate. The reaction MH21-134 is GaI/31-4GlcNAc/313Gal/314GlcNAc01->
was stopped by addition of glycerol (final concentration, 15 mM) and 3Gal/31R. The specificity of this MAb and the structures of
left for 5 min at 0"C. The reaction mixture was then dialyzed overnight
the glycolipids tested in this study are summarized in Table 1.
at room temperature against 0.1 M sodium acetate (pH 5.5). Oxidized In the immunodiffusion test using sheep anti-human Igd,
immunoglobulin preparations were placed in plastic screw-capped tubes IgG:, IgG,, and IgG., (ICN, Lisle, IL), MH21-134 was reactive
containing finely powdered biotin hydrazide (Vectastatin) to a final only with IgG, (data not shown).
concentration of 10 mM, mixed, and reacted with shaking for 2 h at
room temperature. Biotinylated MH21-134 was then dialyzed in PBS
TLC Immunostaining of Neutral Glycolipids Extracted from
overnight at 4C.After washing in 5 mM Tris buffer, pH 7.4, for 20 Various Cancer Tissues by MH21-134. TLC immunostaining
min, the sections were treated for l h with the PBS that contained the of neutral glycolipids extracted from various cancer tissues by
avidin-biotinylated peroxidase complex. After washing in 5 mM Tris MH21-134 indicated that nLc,, and nLcantigens are present
buffer for 30 min, the sections were treated with the substrate that in the glycolipids extracted from some cases of colon cancer
contained 3,3'-diaminobenzidine (Dotile, Tokyo, Japan) for 60 s, (Fig. 3, a and A), breast cancer (Fig. 4, a and b), and lung cancer
washed with water, and weakly counterstained with hematoxylin. Sec (Fig. 4, c and d). As summarized in Table 2, the positive
5690
Downloaded from cancerres.aacrjournals.org on June 28, 2017. 1989 American Association for Cancer Research.
HUMAN IgGj MAb DIRECTED TO AN UNBRANCHED REPEATING TYPE 2 CHAIN
DISCUSSION
2345 2345
The significance of the human MAb approach is several-fold.
Fig. 2. Specificities of MAb MH21-I34 towards various kinds of glycolipid
antigens as ascertained by TLC immunostaining. A, TLC stained with orcinol- One important aspect is the ability to dissect specific host
H2SO4; B, TLC immunostained with MH21-134. Lane I, the neutral glycolipid immune responses, particularly the B-cell repertoire, to various
mixture extracted from human type O erythrocytes serving as a control [lop to
bottom: LacCer. Gb3. Gb4 (major band). nLc4. H,, H2. H,|; lane 2, from top to
types of human cancer. A second significant use of human
bottom. CDH. PG. nLc:lane 3. nLc6: lane 4. SPG. sialosyl-nLiv lane 5, MAbs is to determine the exact epitope structure of human
lactoisooctaosylceramide (I antigen). All quantitites = 1 <*g. cancer that is capable of inducing human B-cell response. This
knowledge will be important to develop effective vaccines
occurrence of nLc,, and nLcwas highest in colon cancer against human cancer. Third, the MAbs themselves will be
(71.4%), followed by breast cancer (66.7%), and lung cancer valuable reagents for imaging of human tumors and suppression
(50%). of tumor cell growth, in cases where antigen expression is highly
In contrast, nLc6 and nLc* antigens were absent in extract of limited to human cancer. This third possibility has been re
normal colonie epithelia, and in extracts of normal pancreas stricted in its application because essentially all known human
and normal kidney. A weak band corresponding to nLcwas MAbs detecting glycolipids on cell surface membranes are of
detected in liver extract, and nLc6 was found in spleen extract, IgM class and have low antigen-binding affinity, particularly at
although these tissues showed negative immunohistology stain 37C.
ing with MAb MH21-134 (see below). A large quantity of both Despite major technical problems in establishing stable
antigens was detected in placenta extract, in agreement with clones that efficiently secrete human MAbs, a number of im
previous findings (21). mortal clones secreting human antibodies directed to tumor-
Immunohistochemical Examination of Various Kinds of Can associated antigens have been established (3-12). Studies have
cers by MH21-134. Colon cancer and hepatocellular carcinoma mainly focused on (a) EBV-transformed B-cell clones from
showed the highest incidence of expression of nLc6 and nLc* cancer patients, (b) lymphocytes of cancer patients fused with
(Fig. 5, b and d), followed by large cell carcinoma of the lung HAT-sensitive mouse myeloma cells, or (c) a combination of
(Fig. 5a), and cancer of the esophagus (Fig. 5c). These results these two approaches. Attempts to establish human/human
5691
Downloaded from cancerres.aacrjournals.org on June 28, 2017. 1989 American Association for Cancer Research.
HUMAN IgGj MAb DIRECTED TO AN UNBRANCHED REPEATING TYPE 2 CHAIN
Table l Structures of various glycosphingolipid antigens used in this study, and their reactivities with human MAb MH2I-34
Fucnl -. 2Gal/3l
G, NeuAc2-. 3Gal/3l
4GlcNAcf(l
"Gal/31 ^4GlcNAc01 -~ 3Gal/31
4Glc/31
ICer
Downloaded from cancerres.aacrjournals.org on June 28, 2017. 1989 American Association for Cancer Research.
HUMAN IgGj MAb DIRECTED TO AN UNBRANCHED REPEATING TYPE 2 CHAIN
nl_c8~ nl_c8
8 9 10 11 12 13 14 15 16 8 9 10 11 12 13 14 15 16
Table 2 Results of TLC immunoslaining study of neutral glycosphingolipid 2 chain. It is important to note that synthesis of unbranched
fractions from various kinds of cancers using MH2I-134
type 2 chain is greatly enhanced due to enhanced l
nLc71%
and/or
3GlcNAc transferase, although \ 3 and l
4 Gal trans-
Colon cancer (8/14) (8/1 4) (10/14)
Lung cancer 50% (4/8) 38% (3/8) 50% (4/8)
ferases are essentially unchanged in colonie tumors (35). Per
Breast cancernLc,57%50% (3/6)nLc,57%67% (4/6)nLc,, 67% (4/6) haps the 01
oGlcNAc transferase, which is responsible for
synthesis of branched type 2 chain, could be competitively
suppressed by the predominance of the l 3GlcNAc trans
antigens are highly expressed in and associated with a variety ferase. The presence of the unbranched, unsubstituted type 2
of human cancers. Surprisingly, staining of normal tissues with chain not only in fetal erythrocytes but also in other fetal tissues
MH21-134 was very limited (Table 3) as compared with stain is assumed, since the structure is known to be reactive with one
ing with antibody NCC-LU-1004, which is also directed to class of anti-i antibodies, which is known to be oncodevelop-
unbranched type 2 chain but reacts strongly with the sialylated mentally regulated (36, 37). In our previous studies, i antigen
derivative (7). Differences in tissue stainability with the anti was detectable in semipurified glycoprotein prepared from six
bodies MH21-134 and NCC-LU-1004 seem to be due to the of eight cases of colonie cancer extracts but was undetectable
lack of reaction of MH21-134 with sialylated unbranched type in the same glycoprotein fraction prepared from five of eight
^'tv r
Fig. 5. Immunohistochemical staining us
ing the MAb MH2I-134. A, large cell carci
v
-- .
noma of the lung; B. well-differentiated ade-
nocarcinoma of the colon; C. poorly differen
tiated squamous cell carcinoma of the
esophagus: D. hepatocellular carcinoma, orig
inal magnification x 160. .
5693
Downloaded from cancerres.aacrjournals.org on June 28, 2017. 1989 American Association for Cancer Research.
HUMAN IgG, MAb DIRECTED TO AN UNBRANCHF.DREPEATING TYPE 2 CHAIN
Table 3 Results of immunohistochemical study of various types of cancers, and normal tissues, using MAb MH2I-I34
tissuesLung
Cancer rate44.4% tissues"Brain rate0',
cancer
Adcnocarcinoma (12/27)
Squamous cell carcinoma 53.8% (14/26) Thyroid gland 0% (0/2)
Large cell carcinoma 58.8% (10/1 7)
carcinomaEsophagus
Small cell (2/11)53.3%
18.2% EsophagusLiverKidneyAdrenal 0%0%0%0%100%
(0/2)(0/2)(0/2)(0/1)(2/2)
cancerGastric (8/15)38.9%
cancerColon 8)64.7%(7/1
Lung
Bronchial gland epithelia 100% (2/2)
Other areas 0% (0/2)
Normal cells*
Lymphocytes 1.1% (1.3%)
Ciranulocytes 86.1% (5.1%)
" Cause of death in normal subjects was automobile accident.
* Analyzed with fluorescence-activated cell sorter; positive cell population expressed as percentage: numbers in parentheses, percentage positive cells in control
without antibody.
75r
I A. B.
MH21-134 antibody Anti-i(Dench) antibody
20
50 100:1
25 o
i? 1.0
5O 5 0.5 O.O5
Antibody Concentrotion (ug/ml)
Fig. 6. Antibody-dependent cytotoxicity of HL-60 cells by MAb MH2I-134. 5 6 1 23456
Percentage target cell lysis is indicated on the abscissa. The three lines represent
different effectortarget cell ratios. II
It-Dip
5. Tai, T., Paulson. J. C.. Cahan. L. D., and Irie. R. F. Ganglioside GM2 as a
REFERENCES human tumor antigen (OFA-1-1). Proc. Nati. Acad. Sci. USA, SO: 5392-
5396. 1983.
1. Hakomori. S., and Kannagi, R. Glycosphingolipids as tumor-associated and 6. Yamaguchi. H.. Furukawa. K.. Fortunato. S. R., Livingston. P. O., Lloyd,
differentiation markers. J. Nail. Cancer Inst., 71: 231-251. 1983. K. O., Oettgen, H. F., and Old. L. J. Cell-surface antigens of melanoma
2. Feizi, T. Demonstration by monoclonal antibodies that carbohydrate struc recognized by human monoclonal antibodies. Proc. Nati. Acad. Sci. USA,
tures of glycoproteins and glycolipids are oncodevelopmemal antigens. Na 4:2416-2420, 1987.
ture (Lond.), 14:53-57, 1985. 7. Schrump. D. S., Furukawa, K., Yamaguchi. H.. Lloyd. K. O.. and Old. L. J.
3. Irie. R. F., Sze, L. L., and Saxton. R. E. Human antibody to OFA-I. a tumor Recognition of galactosylgloboside by monoclonal antibodies derived from
antigen, produced in vitro by Epstein-Barr virus-transformed human fi- patients with primary lung cancer. Proc. Nati. Acad. Sci. USA, 85: 4441-
lymphoid cell lines. Proc. Nati. Acad. Sci. USA, 79: 5666-5670. 1982. 4445. 1988.
4. Cahan, L. D., Irie, R. F., Singh. R.. Cassidenti. A., and Paulson, J. C. 8. Hirohashi. S.. Clausen. H.. Nudelman, E.. Inoue. H.. Shimosato. Y., and
Identification of human neuroectodermal tumor antigen (OFA-I-2) as gan- Hakomori. S. A human monoclonal antibody directed to blood group i
glioside GD2. Proc. Nati. Acad. Sci. USA, 79: 7629-7633, 1982. antigen: heterohybridoma between human lymphocytes from regional lymph
5694
Downloaded from cancerres.aacrjournals.org on June 28, 2017. 1989 American Association for Cancer Research.
HUMAN IgGj MAb DIRECTED TO AN UNBRANCHED REPEATING TYPE 2 CHAIN
nodes of a lung cancer patient and mouse myeloma. J. Immunol., 7.*6:4163- sialosylgalactosylceramide (G7) as a major component. J. Neurochem.. 27:
4168. 1986. 829-839. 1973.
9. Cote. R. J.. Morrissey. D. M.. Houghton. A. N.. Thomson. T. T.. Daly, M. 26. Magnani. J. L., Smith. D. F.. and Ginsburg. V. Detection of gangliosides
E., Oettgen, H. F.. and Old. L. J. Specificity analysis of human monoclonal that bind cholera toxin: direct binding of 1!!I-labeled toxin to thin-layer
antibodies reactive with cell surface and intracellular antigens. Proc. Nati. chromatograms. Anal. Biochem., 709:399-402. 1980.
Acad. Sci. USA, 83: 2959-2963. 1986. 27. Wisecarver, J.. Bechtold. T.. Collins, M.. Davis, J., Lipscomb. H.. Sonna
10. Kozbar. D.. and Roder, J. C. Requirements for the establishment of high- bend, J., and Purtilo. D. T. A method for determination of antibody-
titered human monoclonal antibodies against tetanus toxoid using the Ep- dependent cellular cytotoxicity (ADCC) of human peripheral mononuclear
stein-Barr virus technique. J. Immunol., 127: 1275-1280. 1981. cells. J. Immunol. Meth.. 79:277-282, 1984.
11. James. K.. and Bell. G. T. Human monoclonal antibody production: current 28. Niemann. H., Watanabe, K., Hakomori. S.. Childs. R. A., and Feizi, T.
status and future prospects. J. Immunol. Meth.. 100: 5-40, 1987. Blood group i and I activities of "lacto-A/-norhexaosylceramide" and its
12. Thompson, K. M. Human monoclonal antibodies. Immunol. Today, 9: 113- analogues: the structural requirements for -specificities.Biochem. Biophys.
117. 1988. Res. Commun.. */: 1286-1293. 1978.
13. Yamakawa. T.. and Suzuki. S. The chemistry of lipids of posthemolytic 29. Furukawa, K., Yamaguchi, H., Oettgen, H. F.. Old. L. J.. and Lloyd, K. O.
residue or stroma of erythrocytes: I. Concerning the ether-insoluble lipids of Two human monoclonal antibodies reacting with the major gangliosides of
lyophilizcd horse blood serum. J. Biochem. (Tokyo). 38: 199-212. 1951. human melanoma and comparison with corresponding mouse monoclonal
14. Hakomori. S.. Siddiqui. B.. Li. Y-T., Li, S-C., and Hellerqvist, C. G. antibodies. Cancer Res.. 49: 191-196. 1989.
Anomeric structures of "globoside" and ceramide trihexoside of human 30. Furukawa. K., Yamaguchi. H.. Oettgen, H. F.. Old, L. J.. and Lloyd, K. O.
erythrocytes and -BHK~ fibroblasts. J. Biol. Chem.. 246: 2271-2277. 1971. Analysis of the expression of A'-glycolylneuraminic acid-containing ganglio
15. Siddiqui. B.. and Hakomori, S. A ceramide tetrasaccharide of human eryth- sides in cells and tissues using two human monoclonal antibodies. J. Biol.
rocyte membrane reacting with anti-type XIV pneumococcal polysaccharide Chem.. 263: 18507-18512. 1988.
antiserum. Biochim. Biophys. Acta. 330: 147-155, 1973. 31. Furukawa, K., Chait, B. T., and Lloyd, K. O. Identification of NeuGc-
16. Watanabe, K., Powell. M. E.. and Hakomori, S. Isolation and characteriza containing gangliosides of cat and sheep erythrocytes: "2Cf fission fragment
tion of gangliosides with a new sialosyl linkage and core structure: ganglio- onizationmass spectrometry in the analysis of glycosphingolipids. J. Biol.
sides of human erythrocyte membranes. II. J. Biol. Chem.. 254: 8223-8229. Chem., 263: 14939-14947, 1988.
1979. 32. Furukawa, K., Thampoe. I. J.. Yamaguchi. H., and Lloyd. K. O. The addition
17. Walanabc, K.. Laine, R. A., and Hakomori. S. On neutral fucoglycolipids of exogenous gangliosides to cultured human cells results in the cell type
having long branch carbohydrate chains: H-active glycosphingolipids in specific expression of novel surface antigens by a biosynthctic process. J.
human erythrocyte membranes. Biochemistry. 14: 2725-2733, 1975. Immunol., 142: 848-854, 1989.
18. Watanabe. K., Powell. M.. and Hakomori. S. Isolation and characterization 33. Nowinski. R.. Berglund. C.. Lane. J.. Lostrom, M.. Bernstein, I.. Young. VV.
of a novel fucoganglioside of human erythrocyte membranes. J. Biol. Chem.. W., Jr., Hakomori. S.. Hill, L., and Cooney. M. Human monoclonal antibody
754:8962-8967, 1978. against Forssman antigen. Science (Wash. DC), 210: 537-539, 1980.
19. Kundu. S. K., Samuelsson, B. E., Pascher, 1., and Marcus, D. M. New 34. Tsuji, Y., Clausen. H.. Nudelman. E., Kaizu, T.. Hakomori. S.. and Isojima.
gangliosides from human erythrocytes. J. Biol. Chem., 258: 13857-13866, S. Human sperm carbohydrate antigens defined by an antisperm human
1983. monoclonal antibody derived from an infertile woman bearing antisperm
20. Okada. Y., Kannagi, R.. Levery, S. B., and Hakomori, S. Glycolipid antigens antibodies in her serum. J. Exp. Med.. 168: 343-356. 1988.
with blood group I and i specificities from human adult and umbilical cord 35. Holmes, E. H.. Hakomori. S.. and Ostrander, G. K. Synthesis of type 1 and
erythrocytes. J. Immunol.. 133: 835-842. 1984. 2 lacto series glycolipid antigens in human colonie adenocarcinoma and
21. Taki. T.. Matsuo. K.. Yamamoto, K.. Matsubara. T.. Hayashi. A.. Abe, T.. derived cell lines is due to activation of a normally unexpressed /il N-
and Matsumoto. M. Human placenta gangliosides. Lipids. 23: 192-198. acetylglucosaminyltransferase. J. Biol. Chem.. 262: 15649-15658, 1987.
1988. 36. Watanabe. K., and Hakomori. S. Status of blood group carbohydrate chains
22. Kannagi, R., Stroup, R., Cochran, N. A., Urdal. D. L.. Young, W. W., Jr., in ontogenesis and in oncogenesis. J. Exp. Med.. 744:644-653, 1976.
and Hakomori, S. Factors affecting expression of glycolipid tumor antigens: 37. Kapadia, A., Feizi, T., and Evans, M. Changes in the expression and polari
influence of ceramide composition and coexisting glycolipid on the antige- zation of blood group I and i antigens in postimplantation embryos and
nicity of gangliotriaosylceramide in murine lymphoma cells. Cancer Res., teratocarcinomas of mouse associated with cell differentiation. Exp. Cell
.4997-5005,1983. Res., 131: 185-195, 1981.
23. Kannagi. R., Nudelman, E.. Levery, S. B., and Hakomori, S. A series of 38. Hakomori. S.. and Young, W. W.. Jr. Tumor-associated glycolipid antigens
human erythrocyte glycosphingolipids reacting to the monoclonal antibody and modified blood group antigens. Scand. J. Immunol. Suppl., 6: 97-117.
directed to a developmentally regulated antigen. SSEA-1. J. Biol. Chem.. 1978.
257: 14865-14874. 1982. 39. Otaka. M.. Singhal, A., and Hakomori. S. Antibody-mediated targeting of
24. Folch-Pi. J.. Arsove. S., and Meath. J. A. Isolation of brain strandin, a new differentiation inducers to tumor cells: inhibition of colonie cancer cell growth
type of large molecule tissue component. J. Biol. Chem.. 191:819-831. 1951. in vitro and in vivo: a preliminary note. Biochem. Biophys. Res. Commun..
25. Ledeen. R. VV.,Yu. R. K.. and Eng. L. F. Gangliosides of human myelin: 75:202-208. 1989.
5695
Downloaded from cancerres.aacrjournals.org on June 28, 2017. 1989 American Association for Cancer Research.
Human IgG3 Monoclonal Antibody Directed to an Unbranched
Repeating Type 2 Chain (Gal 14GlcNAc13Gal14GlcNAc
13Gal1R) Which Is Highly Expressed in Colonic and
Hepatocellular Carcinoma
Masayuki Miyake, Nobuoki Kohno, Edward D. Nudelman, et al.
Updated version Access the most recent version of this article at:
http://cancerres.aacrjournals.org/content/49/20/5689
E-mail alerts Sign up to receive free email-alerts related to this article or journal.
Reprints and To order reprints of this article or to subscribe to the journal, contact the AACR Publications
Subscriptions Department at pubs@aacr.org.
Permissions To request permission to re-use all or part of this article, contact the AACR Publications
Department at permissions@aacr.org.
Downloaded from cancerres.aacrjournals.org on June 28, 2017. 1989 American Association for Cancer Research.