Clinical evidences of GM3 (NeuGc) ganglioside expression in human breast cancer using the 14F7 monoclonal antibody labelled with (99m)Tc.
The relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, reasons for considering these molecules as potential targets for cancer immunotherapy and diagnosis. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast tumours. Nevertheless, the lack of a direct evidence of this antigenic display in human breast cancer has kept the subject controversial. For the first time, we described herein the "in vivo" detection of GM3(NeuGc) ganglioside in human breast primary tumours using a radioimmunoscintigraphic technique with 14F7, a highly specific anti-GM3(NeuGc) ganglioside monoclonal antibody, labelled with (99m)Tc. In an open, prospective Phase I/II clinical trial, including women diagnosed in stage II breast cancer, the 14F7 monoclonal antibody accumulation in tumours at doses of 0.3 (n=5), 1 (n=5) and 3 mg (n=4) was evaluated. Noteworthy, the immunoscintigraphic study showed antibody accumulation in 100% of patients' tumours for the 1 mg dose group. In turn, the radioimmunoconjugate injected at doses of 0.3 mg or 3 mg of the antibody, was uptaken by 60 and 33.3% of breast tumours, respectively. "In vivo" immune recognition of GM3(NeuGc) in breast tumours reinforces the value of this peculiar target for cancer immunotherapy.
Oliva
Juan P
JP
Department of Nuclear Medicine, National Institute of Oncology and Radiobiology, Plaza, Havana, Cuba.
Valdés
Zodilina
Z
Casacó
Angel
A
Pimentel
Gilmara
G
González
Joaquín
J
Alvarez
Irene
I
Osorio
Martha
M
Velazco
Milagros
M
Figueroa
Mariela
M
Ortiz
Rosa
R
Escobar
Xiomara
X
Orozco
Maiby
M
Cruz
Julia
J
Franco
Sonia
S
Díaz
Mirtha
M
Roque
Lourdes
L
Carr
Adriana
A
Vázquez
Ana M
AM
Mateos
Cristina
C
Rubio
María C
MC
Pérez
Rolando
R
Fernández
Luis E
LE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005679:G(M3) Ganglioside / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D016719:Radioimmunodetection; D013667:Technetium / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D005679:G(M3) Ganglioside; D013667:Technetium