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Effective antitumor therapy based on a novel antibody-drug conjugate targeting
the Tn carbohydrate antigen
#MMPMID27622021
Sedlik C
; Heitzmann A
; Viel S
; Ait Sarkouh R
; Batisse C
; Schmidt F
; De La Rochere P
; Amzallag N
; Osinaga E
; Oppezzo P
; Pritsch O
; Sastre-Garau X
; Hubert P
; Amigorena S
; Piaggio E
Oncoimmunology
2016[Jul]; 5
(7
): e1171434
PMID27622021
show ga
Antibody-drug conjugates (ADC), combining the specificity of tumor recognition by
monoclonal antibodies (mAb) and the powerful cytotoxicity of anticancer drugs,
are currently under growing interest and development. Here, we studied the
potential of Chi-Tn, a mAb directed to a glyco-peptidic tumor-associated antigen,
to be used as an ADC for cancer treatment. First, we demonstrated that Chi-Tn
specifically targeted tumor cells in vivo. Also, using flow cytometry and
deconvolution microscopy, we showed that the Chi-Tn mAb is rapidly internalized -
condition necessary to ensure the delivery of conjugated cytotoxic drugs in an
active form, and targeted to early and recycling endosomes. When conjugated to
saporin (SAP) or to auristatin F, the Chi-Tn ADC exhibited effective cytotoxicity
to Tn-positive tumor cells in vitro, which correlated with the level of tumoral
Tn expression. Furthermore, the Chi-Tn mAb conjugated to auristatin F also
exhibited efficient antitumor activity in vivo, validating for the first time the
use of an anti-Tn antibody as an effective ADC.
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