ASOURCE Times

Combination of drugs and medical devices

Rakuten Medical Japan last year9Month, cancer topical treatment drug "Acalx^ⓇIntravenous drip250㎎ ”and medical equipment laser device“BioBlade^ⓇObtained manufacturing and marketing approval for both "laser system". The target of treatment is "unresectable locally advanced or locally recurrent head and neck cancer". These are drugs and medical devices that enable breakthrough treatments called photoimmunotherapy.

Acalux is an epidermal growth factor receptor expressed on the surface of cancer cells (EGFR) Targeted antibody to dye (IRDye^Ⓡ700DX) Combined drug. When administered to cancer patientsEGFRHas the property of selectively binding to cancer cells that express. OneBioBladeLaser system wavelength690nmIR700 by irradiating the laser beam ofTo excitePDTSemiconductor laser device. Acarx IR700 bound to the surface of cancer cellsWhen it is excited by laser light irradiation and causes a chemical reaction, it damages the cell membrane of cancer cells and kills the cancer cells.

The antibody portion of Acalx is commonly known as cetuximab and has a track record of being used by major pharmaceutical companies for the treatment of head and neck cancer and colorectal cancer. When using only an antibody, it is possible to suppress the action of molecules that are the key to the growth of cancer cells, or to suppress or kill the growth of cancer cells by activating various immune mechanisms associated with antibody binding. aim. In the case of photoimmunotherapy, cetuximab plays a role in carrying a dye, which is a photosensitizer, and is strong by irradiating a laser beam after binding to cancer cells and activating the dye, which has no pharmacological activity by itself, by excitation. Expected to have anti-cancer effect.

Hit cancer deep in organs with a fine catheter

Photoimmunotherapy cannot be effective for cancers that laser light does not reach due to its principle. In that case, only cancers that can occur on the surface of the body, such as skin cancer and breast cancer, can be treated. Therefore, the developers came up with theBioBladelaser system (photo), which inserts a minute optical fiber into the patient's body and irradiates the affected area with laser light. There are several types, but the diffuser for intra-tissue irradiation has a total length of200cm and a diameter of the irradiated part of0.93 ± 0.07 mm.

Overseas No. 1 for patients with unresectable locally recurrent squamous cell carcinoma of the head and neck who have become refractory to various cancer treatmentsI / IIaPhase testⅡaIn the phase part30In the example, the complete response that makes cancer invisible isFourexample(13.3%), The partial response that was observed to be reduced9example(30%). As a result of targeting a group of patients who did not respond to anticancer drugs, a high therapeutic effect was observed. It is expected that this result will be further improved if treatment can be performed earlier.EGFRSince it is also expressed in esophageal cancer, colorectal cancer, lung cancer, and pancreatic cancer, expectations are high for future expansion of indications. The National Cancer Center Hospital East, which conducted a clinical trial of photoimmunotherapy for head and neck cancer in Japan, has started a clinical trial for esophageal cancer and gastric cancer.

The advantage of this treatment is that it is possible to expand the range of treatment by changing the antibody. This is the emergence of so-called platform-type cancer treatments that can be used to treat many cancers by replacing antibodies that can selectively bind to cancer cells.

BioBlade® Laser System

Heavy ion beam therapy with expanding applications

In addition, the combination of drugs and medical devices is progressing. For example, particle beam therapy.

Radiation includes photon beams, electron beams, and particle beams.3type (figure) Yes, usually photon rays for radiation therapy for cancerXAlthough wires are used, particle beams such as proton beams and heavy particle beams can also be used for cancer. As a feature of particle beam therapy, compared to other radiotherapy, it is possible to concentrate damage on cancer tissue and cause less damage to normal parts.XThe line peaks near the surface of the body andXWhile injuring the skin and surrounding tissues through which the beam passes, the particle beam has a peak dose at a certain depth of the body, and the dose before and after that is weak, so that the dose can be collected in the cancer tissue. In addition, heavy particle beams are heavier than proton beams, so they can cause greater damage to cancerous tissues.

From soccer court to tennis court

However, at present, even with the same particle beam, proton beam facilities are nationwide.17 17While there are several locations, the facilities that can treat cancer with heavy ion beams are the National Institutes for Quantum and Radiological Science and Technology, National Institutes for Quantum and Radiological Science and Technology.QSTWe only count 6 locations such as hospitals (Chiba City) and Hyogo Prefectural Particle Beam Medical Center (since we are planning to do so in Yamagata and Okinawa, we will soon be nationwide.8It will be in one place).

This is because heavy ion radiotherapy requires a large-scale facility and a huge amount of electric power, which is a bottleneck for its widespread use. However, the National Institutes for Quantum and Radiological Science and Technology is developing ultra-compact superconducting synchrotrons and laser-driven ion-accelerated injectors, and the current equipment is the soccer court.1It requires a lot of land, but once those technologies are completed,20m× 10mIt is enough to have the area of the area, that is, the area of the tennis court. With further research, there is ample room for downsizing, and it is no longer a dream for each of the regional core hospitals to own a heavy ion beam device.

Combination of heavy ion beam and immunotherapy

At present, surgery is the main treatment for cancer, but since the number of elderly patients is increasing recently, it is expected that the number of cases of choosing heavy ion beam will increase in the future, avoiding highly invasive surgery. Also before surgeryXThere are an increasing number of cases in which surgery is performed by irradiating a line or heavy particle beam to reduce the size of the cancer and then narrowing the range, and the combination of the characteristics of each treatment method is becoming the frontier of cancer treatment.

1994The National Institute of Radiological Sciences, which has been conducting heavy ion radiotherapy in Japan since 2014, has started research on the combined use of heavy ion beam and immune checkpoint inhibitors. For this purpose1First, when the cancer is irradiated, shrinkage or disappearance is observed even in the unirradiated cancer, which enhances the abscopal effect. The Abscopal effect is said to be a phenomenon in which the antigen of cancer cells that are damaged by irradiation and released into the blood induces the immune response of the patient, and the cancer cells that have not been irradiated are also attacked by the immune cells. .. This principle is expected as a new principle of radiation therapy, but its frequency is very rare. This is because the immune response to cancer cells is thought to be inhibited by the immune escape mechanism. Therefore, the aim is to release this immune escape mechanism by using an immune checkpoint inhibitor.

Ceranostics aiming at therapeutic and diagnostic drugs at the same time

It is a new idea of seranostics to dispel the stereotype that therapeutics and diagnostics are developed by different companies. It is a coined word of therapy (treatment) and diagnostics (diagnosis), and Germany is ahead in this field. In Germany, particle beams are attached to peptides that specifically bind to prostate cancer.1Is a seedαStudies are being attempted to treat patients with advanced prostate cancer with drugs that combine rays-emitting atoms (radionuclides). Cases in which prostate cancer that has metastasized to the whole body have completely disappeared have also been reported and are attracting attention.

Radionuclides are often used for diagnosis. Proton beam tomography, so-called, that is taken up by cancer cells and detects the presence of minute cancers.PETIt's an inspection. It uses a compound labeled with a radionuclide on glucose, which cancer cells prefer to absorb, as a contrast agent. If the radiation emitted by this radionuclide has the effect of attacking cancer cells, it will be possible to make an accurate diagnosis and selectively treat the cancer cells. Theranostics born from such an idea is attracting attention as an innovative cancer treatment principle.

Nihon Medi-Physics, a leading manufacturer of radionuclides2019In 2014, he established the "Ceranostics Development Center" in Sodegaura City, Chiba Prefecture, and has entered the development of cancer treatment drugs. Traditionally, it is relatively easy to handle when treating cancer with radiation nuclidesβLines were the mainstream, but Nihon Medi-Physics has a large amount of radiation damage and energy.αFocus on the development of seranostics using wires. If this technology is established, it will be possible to replace antibodies and peptides and apply them to the treatment of various cancers, similar to photoimmunotherapy.

In the 21stcentury, molecular-targeted therapies and immune checkpoint inhibitors have appeared, and cancer treatment has made great strides. However, the results of the drug alone are approaching their limits. In the future, innovations in medical devices are likely to drive not only cancer diagnosis but also treatment.