Within an international collaboration of the IAEA we performed biodistribution studies and an experimental radionuclide therapy in a CCK2R-specific mouse tumour model using two 177Lu-labelled cyclic minigastrin-analogues: DOTA-cyclo[γ-D-Glu-Ala-Tyr-D-Lys]-Trp-Met-Asp-Phe-NH2 (DOTA-cyclo-MG1) and DOTA-cyclo[γ-D-Glu-Ala-Tyr-D-Lys]-Trp-Nle-Asp-Phe-NH2 (DOTA-cyclo-MG2).
The immunological status of animals with small and large tumours was examined and it was shown that mice with 1·0 g tumours have unimpaired mitogen responsiveness and measurable tumour specific immunity, whereas mice bearing large tumours (2·5 g) have a markedly impaired immune system.
Based at the University of Washington in St Louis, Levi-Montalcini demonstrated that the dramatic changes to the number and pattern of nerve cells in chick embryos, induced experimentally by the local grafting of mouse tumour cells, were caused by a specific chemical – a protein – produced by the tumour cells.
Anti-mouse antibodies form complexes with the tumour specific antibody, which are rapidly cleared from the circulation so preventing tumour localisation.
Importantly, in vitro treatment with rPDCD1 fragment did not affect the viability of mouse tumour cells (Fig 4C), implying that in tumour bearing mice, a vast number of tumour-specific exhausted CTLs exist that can be immediately reactivated by PDCD1/PD-L blockage, leading to cytolysis of the tumour.
Tumour specific vHMEC DMRs.
When splenocytes from mice treated with DC-based immunotherapy were co-cultured with tumour cells a massive induction of tumour lysis was observed, demonstrating that DC-based immunotherapy induces tumour specific recognition by immune cells.
It now seems likely that the loss of heterozygosity (LoH) occurred through recombination, although chromosome loss may also have contributed, as previously recorded in long-transplanted "non-specific" mouse tumours by Sachs and Gallily and by Hauschka and Levan, in early work cited in [ 2].
A large amount of knowledge about mutations, oncogenes, impaired tumour suppressor pathways, growth factors, epigenetics and so on, is more or less specific for human tumours and much less is known about the effects of these factors in mouse tumours.
