Efficacy and specificity of a monoclonal antibody-drug conjugate in chemotherapy by intratumoral injection.

The murine monoclonal antibody (Mab) A7 conjugated to neocarzinostatin (A7-NCS) was injected intratumorally (IT) into tumor bearing nude mice. Its pharmacokinetics and tumoricidal effects were compared in the high, moderate and low antigen expressing xenograft for SW1116, WiDr and KB tumor-bearing nude mice, respectively. When injected IT into nude mice, [125I]A7-NCS was retained in the tumors according to the degree of antigen expression; it was also disseminated into the blood inverse proportion to the antigen expression. Addition of an excess amount of Mab A7 reduced [125I]-A7-NCS accumulation in SW1116 xenograft and elevated the [125I]A7-NCS concentration in the circulation. Complete tumor reduction was found in all 5 mice with SW1116 tumor, and 2 of 5 mice with WiDr tumor. However, only incomplete tumor suppression was observed in mice with the KB tumor. The significant tumor reduction in SW1116 bearing nude mice was attenuated when excess of Mab A7 was simultaneously administered with A7-NCS. These findings indicate that A7-NCS was localized in the target tumors and exerted its tumoricidal effects depending on the degree of antigen-antibody interaction when administered IT. Thus, A7-NCS can be used successfully in vivo for local therapy, auguring new and promising applications for local cancer therapy.

Urinary pepsinogen I as a tumor marker of stomach cancer after total gastrectomy.

The possibility that urinary pepsinogen I is a tumor marker of stomach cancer after total gastrectomy was examined. To decide the cutoff level of urinary pepsinogen I after total gastrectomy, urine samples from 15 patients who had undergone total gastrectomy for stomach cancer in the early or advanced stages and had been free from recurrence for more than 5 years were examined by pepsinogen I-specific radioimmunoassay. The mean concentration of urinary pepsinogen I was 17.5 +/- 7.4 ng/ml and the cutoff level of urinary pepsinogen after total gastrectomy was set at 32 ng/ml (mean + 2 SD). Twenty-two of 74 cases who had undergone total gastrectomy for stomach cancer were regarded as positive. And 20 of these 22 positive cases had definite clinical signs of recurrence of stomach cancer. There were only two false-positive cases. These results suggest that urinary pepsinogen I will be an useful tumor marker in detecting the recurrence of stomach cancer after total gastrectomy.

[Immunoresponses and efficacy after arterial infusion of immunoconjugate A7-NCS in patients with colon cancer].

We prepared an immunoconjugate, A7-NCS, of a mouse-derived anti-human colon cancer monoclonal antibody A7 and the macromolecular protein anticancer agent neocarzinostatin (NCS), and evaluated changes in human anti-mouse antibody (HAMA) by ELISA in the serum of patients intraarterially administered this agent. IgG and IgM class HAMA were detected in all patients, but no IgE class HAMA. In patients with stage V disease, the survival rate was higher in a group treated with A7-NCS at an NCS dose of 4,000 units or more than in that treated at an NCS dose of less than 4,000 units. In these patients, the survival rate was higher in a group treated with A7-NCS at an NCS dose of 4,000 units or more than in one not treated with it. These results suggest the usefulness of A7-NCS administration at high dose for prolonging survival of patients with advanced colon cancer.