High Dose Radiation Inducing Anti-Tumor T Cell Immunity
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Solution Overview
Problem
Current cancer treatments, including stereotactic body radiation therapy (SBRT), are not effective for many types of cancers or cancer stages, necessitating the development of improved regimens for cancer therapy.
Innovation Solution
The method involves administering an initial localized high single dose or short course of radiation to a tumor site, followed by the collection and reinfusion of activated T cells after a sufficient activation period, combined with chemotherapy, to achieve durable complete remission and prevent metastases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high single dose radiation is administered to tumor site, then local control and anti-tumor immunity is improved, but systemic toxicity and damage to surrounding normal tissues increases
Solution Approach 1:
The patent applies localized high-dose radiation therapy (LHIORT) that delivers extremely high radiation doses (e.g., 80-100 Gy) specifically to the tumor site while sparing surrounding normal tissues through precise spatial targeting. This creates a local quality difference where the tumor receives lethal radiation doses while adjacent healthy tissues receive minimal exposure, resolving the contradiction between achieving reliable local control and minimizing toxicity to normal tissues.
Solution Approach 2:
The patent employs preliminary collection and cryopreservation of autologous T cells from the patient before high-dose radiation treatment. These T cells are harvested, stored, and then reinfused after radiation therapy to enhance and sustain the anti-tumor immune response. This preliminary action prepares the immune system in advance to effectively combat tumor cells following the damaging radiation exposure, thereby improving anti-tumor immunity while allowing aggressive local radiation dosing.
2Duration of action of moving object
If conventional radiation therapy is used, then treatment duration is extended, but tumor control efficacy decreases
Solution Approach 1:
The patent employs hypofractionated radiation delivery where the total radiation dose is administered in fewer, larger fractions rather than conventional daily small fractions over many weeks. For example, high doses are delivered in 3-5 fractions over 1-2 weeks instead of 25-35 fractions over 5-7 weeks. This periodic action with larger intervals between treatments maintains tumor control efficacy while significantly reducing overall treatment duration and improving patient convenience.
Solution Approach 2:
The patent fundamentally changes the radiation dosing parameters by administering extremely high single doses (80-100 Gy) or hypofractionated high doses, compared to conventional fractionated doses of 1.8-2.0 Gy per session. This parameter change in dose intensity and fractionation schedule achieves superior tumor control with shorter treatment courses, directly resolving the contradiction between treatment duration and tumor control efficacy.
3Reliability
If T cells are collected and reinfused after radiation, then anti-tumor immunity is enhanced, but treatment complexity increases
Solution Approach 1:
The patent utilizes the patient's own autologous T cells collected from their peripheral blood before radiation treatment. These self-service T cells are cryopreserved and then reinfused after radiation to enhance the anti-tumor immune response. By using the patient's own immune cells rather than allogeneic donor cells or engineered cell lines, the treatment enhances immunity while avoiding the complexities of HLA matching, graft-versus-host disease prevention, and complex cell manufacturing processes.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach induces systemic anti-tumor immunity, leading to complete remissions in primary tumors and prevention of metastases, with the activated T cells being capable of transferring immunity to adoptive hosts, significantly improving survival rates in advanced and metastatic cancers.
Implementation Method 1
localized, high single dose or short courses of high doses of radiation at a tumor site
Implementation Method 2
a dose of chemotherapy, which may be a conventional or a myeloablative dose
Data Source
AI summary
Cancer treatment is provided, by irradiating an individual with a localized, high single dose or short course of doses at a primary tumor site; collecting T cells from the individual after a period of time sufficient activation of an anti-tumor response; treating the individual with an effective dose of dose of chemotherapy; and reintroducing the T cell population back to the individual.