There are many observations in melanoma lesions where the immune system is able to act against the tumours and usually this is a sign of a good prognosis. However, over time the balance is shifted in favour of the tumours.
All this suggests that vaccination for cancer immune therapy, which targets specific tumours could be a possibility in such cases. Current vaccination in cancer is primary a therapeutic intervention rather than prevention like the case with infections diseases. Preventive vaccination against cancer is not possible yet in humans.
But before we consider that type of vaccination there is a need to identify different vaccination strategies for cancer immune therapy and also identification of effective mechanisms used by the immune system.
Hybrid cell vaccination is one of these strategies that use the patient’s tumour cells as antigen and turn them into potent T cell stimulators by fusion with antigen-presenting cells (APCs) such as dendritic cells (DCs).
There are over 250 tumour-associated T cell epitopes derived from about 60 different proteins and majority of the antigens were identified for melanoma and are MHC class I-restricted. Some of these antigens identified in melanoma were later on identified in other tumours.
Cytotoxic T cells with specificity for differentiation antigens are not supposed to exist, as they should have been eliminated during the establishment of self-tolerance. However, they are observed in cancer patients and even healthy individuals. One potential explanation is that these antigen receptors might be of low avidity and in this case the T cells will also have too low efficiency to eliminate the tumour cells.
T cell epitopes specific to tumour cells would be ideal for immune therapy, however very few have been identified in cancer patients so far.
What kind of clinical data is available?
There are number of clinical trials using hybrid cell vaccination strategy that have shown promising results although the patient population were mostly stage IV. A vaccine prepared by fusion of autologous tumour cells with allogeneic activated B cells and given intracutaneously or intradermally have cause turmour response in 3 our of 13 patient with renal cell carcinoma and in 2 our of 16 patients with metastatic melanoma while 5 others had stable disease. Interestingly stable disease was maintained for more than 2 years for some patients.
Another study with allogeneic DCs and autologous tumor cells was completed with 17 patients with metastatic renal cell carcinoma. 4 of the patients had complete response; 2 patients – partial responses and 1 patient – mixed response. Some of the common side effects observed in these studies are: erythema at the sites of inoculation, some cases of fever and others of strong but temporal perspiration. Generally, toxicity is low.
While the results are promising more information is needed to support therapeutic use of hybrid cell vaccination.
Published on 1 Oct 2019
Author: Olga Peycheva, Director at Solutions OP Ltd. Olga has been working in clinical research since 2005 and has extensive experience in Eastern and Western Europe