Abstract
A next generation approach to cancer envisions developing preventative vaccinations to stimulate a person's immune cells, particularly cytotoxic T lymphocytes (CTLs), to eliminate incipient tumors before clinical detection. The purpose of our study is to quantitatively assess whether such an approach would be feasible, and if so, how many anti-cancer CTLs would have to be primed against tumor antigen to provide significant protection. To understand the relevant dynamics, we develop a two-compartment model of tumor-immune interactions at the tumor site and the draining lymph node. We model interactions at the tumor site using an agent-based model (ABM) and dynamics in the lymph node using a system of delay differential equations (DDEs). We combine the models into a hybrid ABM-DDE system and investigate dynamics over a wide range of parameters, including cell proliferation rates, tumor antigenicity, CTL recruitment times, and initial memory CTL populations. Our results indicate that an anti-cancer memory CTL pool of 3% or less can successfully eradicate a tumor population over a wide range of model parameters, implying that a vaccination approach is feasible. In addition, sensitivity analysis of our model reveals conditions that will result in rapid tumor destruction, oscillation, and polynomial rather than exponential decline in the tumor population due to tumor geometry.
Highlights
The most effective way to treat a disease is to prevent its development in the first place
An innovative approach to treating cancer envisions developing preventative anti-cancer vaccines to train a person’s immune cells to eliminate early-stage tumors close to genesis. The design of such a treatment strategy requires an understanding of the tumor and immune interactions leading to a successful anti-cancer immune response
We formulate a mathematical model of the immune response against incipient tumours consisting of as low as hundreds to thousands of cancer cells, which is far below the clinical detection threshold of over 100,000 cells
Summary
The most effective way to treat a disease is to prevent its development in the first place. A generation approach to cancer treatment envisions developing preventative cancer vaccines that would train a person’s immune response to eliminate tumors near inception by stimulating a person’s immune system, especially cytotoxic T lymphocytes (CTLs), to attack cancer cells expressing tumor-associated antigens [1]. Such an immune response would destroy developing tumors close to genesis, before tumor cells have acquired the ability to suppress immune responses or metastasize to other tissues. There are several conceivable obstacles that could hinder a memory anti-tumor CTL response from being effective. The aim of this paper is to assess the feasibility of preventative cancer vaccines from a quantitative perspective
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