Enhancement of the thermal response of murine tumour and normal tissues by a streptococcal preparation, OK-432 (Picibanil)

Abstract

We have studied the effect of a streptococcal preparation, OK-432, given alone or in combination with hyperthermia on murine tumour and normal tissues. The experimental tumour was a spontaneous non-immunogenic fibrosarcoma FSa-II transplanted in the foot of C3Hf/Sed mice. Local hyperthermia was achieved by immersing the mouse foot into a constant temperature water bath (42–45°C) for various lengths of time. Tumour response was studied by analysing the tumour growth (TG) time. Various doses of OK-432 (1–5 KE/mouse) were injected locally into the tumour. Local administration of OK-432 alone (without hyperthermia) had no effect on the TG time. Thermal enhancement ratio (TER) for combined treatment was independent of drug dose ⩾2 KE, and the mean TER was 1.48± 0.27 (95 % CL). The TER was greater for 6 mm tumours than for 4 mm tumours, and it was greatest if the time interval between hyperthermia and drug administration was 3 h or less. There was no effect if the drug was administrated 4 days before hyperthermia, but its application 9 days prior to hyperthermia caused a slight prolongation of the TG time of non-heated tumours, and a reduction in the TG time of heated tumours. Normal-tissue response was studied by scoring the peak foot reaction and RD₅₀ (the treatment time to induce a specified response in one-half of the treated animals). The effect of OK-432 on the thermal response of the foot was also studied at various temperatures. The mean TER was 1–11±0–07. Local administration of OK-432 failed to modify significantly the kinetics of thermotolerance. Present experiments demonstrated that OK-432 after local administration enhanced the thermal response of murine tumour and normal tissues. This enhancement was greater for the tumour than for the normal tissue, resulting in a favourable differential effect between normal and malignant tissues (the average therapeutic gain was 1.33±0.19).

Key Words:

• OK-432
• Picibanil
• hyperthermia
• biological response modifiers
• mouse fibrosarcoma