Immunotherapeutic effect of alpha radiation in syngeneic tumor models
. The purpose of the experiment/project:
The purpose of this experiment is to investigate mechanisms of immune response activation by antibody-targeted alpha radiation in allograft cancer models and mechanisms for acquiring a memory effect.
II. The expected adverse effects on the animals:
Three main adverse effects for the mice in this experiment are ulcerations of the tumors, weight reduction and reduction in white blood cell count. To eliminate the adverse effects, we will daily follow the mice well-being, sacrificing the animals with the first signs of ulcer or 15% weight reduction. White blood cell count didn't lead to any noticeable change in animal well-being. Else, animals will be immediately sacrificed with first signs of distress.
III. The expected scientific benefits or benefits for society:
Previous studies have shown that antibody-targeted alpha radiation has therapeutic effect in nude mice. The immune system present in syngeneic mice can enhance the therapeutic effect of such treatments. Combination therapy of known anti-cancer drugs with different molecules effecting immune system lead to multiple new treatment regimes and dramatic increase in patient survival for many types of cancer.
IV. The number of animals and species:
In this study we aim to investigate temporal changes in activated T-cells following treatment with 2 different test items. In total we aim to use 480 mice.
V. How will the requirements for 3R be accomplished by the experiment/project:
Multiple in vitro studies were conducted to prove the efficacy and specific killing of selected tumor models, as well as extensive characterization of the models was performed. We have already acquired promising data in the same model, thus we have good knowledge of this model with regards to group size, timing of treatment etc. Technicians conduction the study have long experience with similar studies using well refined techniques.
The purpose of this experiment is to investigate mechanisms of immune response activation by antibody-targeted alpha radiation in allograft cancer models and mechanisms for acquiring a memory effect.
II. The expected adverse effects on the animals:
Three main adverse effects for the mice in this experiment are ulcerations of the tumors, weight reduction and reduction in white blood cell count. To eliminate the adverse effects, we will daily follow the mice well-being, sacrificing the animals with the first signs of ulcer or 15% weight reduction. White blood cell count didn't lead to any noticeable change in animal well-being. Else, animals will be immediately sacrificed with first signs of distress.
III. The expected scientific benefits or benefits for society:
Previous studies have shown that antibody-targeted alpha radiation has therapeutic effect in nude mice. The immune system present in syngeneic mice can enhance the therapeutic effect of such treatments. Combination therapy of known anti-cancer drugs with different molecules effecting immune system lead to multiple new treatment regimes and dramatic increase in patient survival for many types of cancer.
IV. The number of animals and species:
In this study we aim to investigate temporal changes in activated T-cells following treatment with 2 different test items. In total we aim to use 480 mice.
V. How will the requirements for 3R be accomplished by the experiment/project:
Multiple in vitro studies were conducted to prove the efficacy and specific killing of selected tumor models, as well as extensive characterization of the models was performed. We have already acquired promising data in the same model, thus we have good knowledge of this model with regards to group size, timing of treatment etc. Technicians conduction the study have long experience with similar studies using well refined techniques.