Anti‐tumor activity of T‐2 toxin‐conjugated A7 monoclonal antibody (T‐2‐A7 MoAb) against human colon carcinoma

Abstract

Monoclonal antibody A7 (A7 MoAb), from splenocytes of a mouse immunized against human colorectal carcinoma, was used as a T-2 toxin (T-2) carrier targeting colon cancer. T-2 was converted to T-2 hemiglutarate by glutaric anhydride treatment, and T-2-A7 MoAb conjugates containing up to 20 T-2 per antibody molecule were obtained from the antibody and T-2 hemiglutarate activated with N-hydroxysuccinimide. The in vitro cytotoxicity against human colon cancer (LS174T) cells indicated that the conjugates were markedly less toxic than the toxin itself. The immunoreactivity was evaluated from the in vitro binding activity of A7 MoAb with LS174T cells, and from the in vivo localization in LS174T-bearing nude mice; it remained essentially intact after conjugation with T-2. The efficacy of the T-2-A7 MoAb conjugate was tested against LS174T-bearing nude mice. The conjugate significantly suppressed the growth of the tumor in comparison with both phosphate-buffered saline and free T-2. These results suggest that the conjugate of T-2 with A7 MoAb might be useful as a selective immunotoxin for cancer immunotherapy, with less serious side effects than T-2.

Preparation of T‑2 toxin‑containing pH‑sensitive liposome and its antitumor activity

“…Studies on targeted agents appear to be the only solution. attempts have been made to prepare T-2 toxin-conjugated antibody drugs, but no substantial progress has occurred (43). as a novel type of nano drug carrier, pH-sensitive liposomes have been widely studied in tumor therapy for their advantages of tumor-targeting and sustained release (44).…”

Análise da prospecção tecnológica por meio de revisão sistemática seguida de meta análise das patentes do gênero Baccharis

“…Como mostrado anteriormente, a partir da década de 80, vários estudos demostram que os tricotecenos, em especial os tricotecenos macrocíclicos, apresentam grande potencial no tratamento de doenças carcinogênicas nas quais foi possível observar resultados promissores para células HepG2, A549, PANC-1 e HL-60 (SU et al, 2013;MURAKAMI et al, 2001;WOLDEMICHAEL et al, 2012;KOJIMA et al, 1993).…”

Revisión: Implicaciones toxicológicas y nutricionales de la toxina T-2 / Review: Toxicological and nutritional implications of T-2 toxin

“…Tienen lugar un aumento significativo de asoclaci6n de la toxina con las celulas, y una disminuci6n en la velocidad de disociaci6n en presencia de los esteroides(Middlebrook y Leatherman, 1989).Se ha desarrollado un anticuerpo monoclonal, el AoMb, que tiene la capacidad de neutralizar totalmente la citotoxicidad de la T-2 en cultivo de linfocitos humanos, por lo que se propone su uso clinico en profilaxis y terapias de toxemia de T-2(Minervini et al, 1994). Ha sido posible formar el complejo innllll1otóxico denominado A7-T-2, que ademas de disminuir la toxicidad no selectiva de la micotoxina, puede concentrar potencialmente la toxina en las celulas diana, observ6ndose en pacientes tratados in vivo una disminucion significativa en el crecimiento de tumores de colon, sin que se produjeran efectos colaterales como la p6rdida de peso(Kojima et al, 1993).Cuando se incluyeron antioxidantes (selenio, alfa tocoferol y 6cido asc6rbico) en la dieta de ratas, se observ6 una disminucion en los efectos causados por la toxicosis de DON y T-2(Rizzo et rrl., 1994). En nuestro laboratorio hemos observado que cuando se incuban hepatocitos de pollo en presencia de la toxina T-2 y carotenoides como la luteina o el licopeno, es posible disminuir hasta en un 50% el efecto citot6xico de esta micotoxina.…”