IMMUNOTHERAPY
CANCER IMMUNOTHERAPY
· DENDRITIC CELL VACCINE
· CYTOKINE INDUCED KILLERS
INTERACTION BETWEEN CANCER AND THE IMMUNE SYSTEM
ERADICATION
The immune system is unquestionably related to cancer formation, development and progression. It is believed that cancer cells can emerge at any time during the lifetime, especially with ageing. However, the components of the antitumor immune response eliminate them without any harmful effects to the organism.
EQUILIBRIUM
Some cancer cells may possess immune resistance mechanisms that enable them to avoid of being noticed by the human immune system. In such cases, the malignant cells are not eliminated, however the immune system is still capable of keeping them under control to prevent the formation of a detectable tumour. In such case, a dynamic balance settles between tumour cells and the components of the immune system. The malignant cells are not completely destroyed, but remain under strict control of the immune system, which suppress the development of clinically relevant tumours. Such state of balance between tumour cells and the immune system can last over decades or even a lifetime without any signs of malignant disease.
EVASION
However, if the tumour cells tend to be more malignant and aggressive, the immune system may not be capable to destroy them completely. During the equilibrium phase, some tumour cells can acquire more potent and sophisticated molecular and cellular mechanisms enabling them to avoid the control of the immune system. At this phase of immune evasion cancer cells form a tumour, which can already be detected by diagnostic procedures and eventually becomes evident clinically.
TUMOR IMMUNOTHERAPY - HELPING THE IMMUNE SYSTEM IN TO FIGHT CANCER
In recent years, immunotherapy has become an essential component of cancer treatment besides current standard therapies. In order to restore the ability of the immune system to control cancer, it is necessary to modulate its activity by applying tumour immunotherapy. There are many immunotherapeutic approaches and therapeutic cancer vaccination is one of the most promising among them. By applying cancer vaccination, it is sought to ensure the long-term anti-tumour immune response, which protects the organism from cancer renewal its progression (metastases and spread in the body). Furthermore, therapeutic cancer vaccination is expected to induce long-term memory immune responses, which have to prevent a relapse or progression of cancer or increase the sensitivity of the tumour cells to subsequent standard cancer treatment methods, such as radiotherapy, chemotherapy, hormone therapy, etc.
REMARK
Assessment of the justification and application of immunotherapy for carcinoma is individual. Patients should make an appointment for an examination at the Polyclinic, take all findings with them and do additional processing if necessary for inclusion in the immunotherapy procedure. The price of immunotherapy depends on which immunotherapy will be performed. It is also necessary to sign an informed consent for the therapy.
IMMUNOTHERAPY WITH DENDRITIC CELLS VACCINES (DCV)
Specific active immunotherapy with dendritic cell vaccines is an innovative, potent form of cancer immunotherapy that has clinically relevant mechanisms of action with great potential for the systematic treatment of cancer. Its aims to reprogram the anti-tumour immune response from of cancer accepting (tolerogenic) to cancer destroying (immunogenic) state. DCV does not directly affect the cancer: the therapeutic effect is instead caused by “nurturing” the immune system so that rather than tolerating the cancer cells, it recognizes them and takes actions to control their activities.
The active ingredients in this vaccine are dendritic cells designed to activate the patient’s immune system to restore their body’s ability to control the activities of cancer cells. Immunotherapy with a dendritic cell vaccine is a personalized cancer therapy, whose applicability particular patient is determined by various factors, including the patient’s general health status and comorbidities, cancer stage, as well as standard treatment strategy.
ACTIVE IMMUNOTHERAPY
In contrast to chemotherapy, most active immunotherapeutic agents such as DCV do not have direct killing activity on cancer cells, but rather act indirectly by reprogramming the antitumor immune response from the state of immune tolerance to a state of immune-mediated control of cancer. This is a dynamic multiphase process that aims at restoring and establishing immune competence of antitumor immunity. Therefore, it requires much more time to establish a meaningful disease control (complete or partial tumour shrinkage or permanent stable disease). Thus, the onset of clinical effect of many immunotherapeutic approaches is often delayed and can take up to 6-9 months to become evident.
PRODUCTION PROCESS
Dendritic cells are collected from patients’ blood, loaded with tumour antigens and matured in a specially designed GMP laboratory WHICH meets strict quality control and surveillance requirements. Once loaded with tumour antigens and matured correctly, the dendritic cells are being activated to induce an immune response when injected back into the patient’s bloodstream. DCVs are made within 4 weeks from the day of blood collection.
Since 2018, JSC Froceth (www.Froceth.lt) has permission to produce not only autologous but also allogeneic dendritic vaccine which are eligible for any type of solid tumour including melanoma, breast, ovarian, lung, cervical, prostate, colorectal, brain cancer, etc. the blood for vaccine production may be taken not only from the patient itself, but also from his first – degree relative (parent or child). In this case, an allogeneic dendritic cell vaccine is produced. This method is especially useful in cases where the patient cannot donate blood, for example after chemotherapy when he encounters low blood count.
PASSIVE IMMUNOTHERAPY, CYTOKINE-INDUCED KILLER (CIK)
Cytokine-induced killer (CIK) cells are currently emerging as a promising and effective treatment option, especially when combined with standard therapy in an adjuvant treatment setting, but can successfully be used as a monotherapy as well. Unlike active immunotherapy with DCV, cytokine-induced killers have a direct killing effect on tumour cells, which in general can be termed as passive immunotherapy. A large number of clinical trials demonstrated encouraging results and showed that CIK cells may prevent recurrence, improve the progression as well as overall survival enhancing quality of life in cancer patients.
CIK cells are a mixture of T-lymphocytes, which are ex vivo expanded with cytokines, comprising CD3+/CD56+ cells, CD56+ natural killer (NK) cells, and CD3+ cytotoxic T cells. Among them, CD3+/CD56+ T cells, which are rare in uncultured peripheral blood, are the main effector cells. They have high proliferation rate, potent antitumor effects with the dual – functional capability of both T-cells and NK-cells, and little cytotoxicity to normal cells, but with substantial specificity to tumour cells.
CIK cells are not restricted to tumour type or origin, therefore can be used for treatment of patients with any diagnosis, as long as it is done in autologous regime. Once reintroduced into the patient’s body, CIKs home in onto the tumour site to kill cancer cells directly. They are able to sense the tumour by danger signals sent by the patient’s body. Their action is immediate, because they are applied in a fully developed state. They do not need any assistance from the patient’s own immune system, which makes this therapy available to patients whose immune systems are too weak to contribute to an effective immune response. This puts CIKs in the category of passive immunotherapy, as they substitute for the patient’s immune system, rather than utilize it.
CIKs are expanded from the patient’s peripheral blood mononuclear cells and are able to proliferate rapidly with the timed addition of cytokines, such as interleukin 2, interferon gamma, and anti-CD3 monoclonal antibodies in vitro. All CIK cell cultures are tested for contamination (bacteria, fungi, mycoplasma) throughout the manufacturing process to assure culture quality and transfusion safety. CIK are manufactured within 4 weeks from the day of blood collection.
COMBINED THERAPY - THE KEY TO SUCCESS
It was shown that active participation of the immune system in the destruction of malignant cells is crucial for the therapeutic effect of chemotherapy, radiation therapy, as well as hormone therapy and many targeted therapies. There is data that chemotherapy and radiotherapy increase the response of cancer to immunotherapy and vice versa. Thus, it is very likely that even if the disease returns during or after immunotherapy treatment, the beneficial effect of immunotherapy still remains because it should increase the response of the tumour to the next line of treatment, mainly chemotherapy. Based on these data, the concept of chemoimmunotherapy is proposed, which states that a judicious combination of immunotherapy with other cancer treatment approaches is necessary to achieve significant and long-term cancer control.
Passive immunotherapy, such as CIK, combines well with active immunotherapy, such as DCV, which mobilizes the patient’s immune system. Such a combination has the advantages of the immediate effect of the passive therapeutic side and the long-term effect that develops during the active immunotherapeutic side. Immunotherapies with CIK and DCVs are an advanced combination therapy since they work on several different principles, contributing to a broad, complex immune response against cancer.
EXOSOMS can be administered in the form of a short i.v. infusion or as an injection. These are microvesicles with anti-tumour and regenerative potential, proven in vitro and in vivo studies as an additive to potentiate DCV
and CIK.
• immunotherapy with DCV and CIK is not yet a standard cancer treatment, but it can be used as an additional advanced therapy
• immunotherapy with DCV and CIK can be used as adjuvant or palliative treatment of various malignant diseases
• immunotherapy with DCV and CIK is a personalized cancer therapy, the applicability of which to an individual
patient is determined by various factors, including:
– general health condition and concomitant diseases of the patient
– stage of cancer
– standard treatment strategy
• immunotherapy with DCV and CIK can be combined with chemotherapy,
hormone therapy, targeted therapy, radiotherapy or other immunotherapy methods
• DCV and CIK immunotherapy is applied by a multidisciplinary team of oncologists and immunologists, together with
standard treatment or after its completion.
It was shown that active participation of the immune system in the destruction of malignant cells is crucial for the therapeutic effect of chemotherapy, radiation therapy, as well as hormone therapy and many targeted therapies. There is data that chemotherapy and radiotherapy increase the response of cancer to immunotherapy and vice versa. Thus, it is very likely that even if the disease returns during or after immunotherapy treatment, the beneficial effect of immunotherapy still remains because it should increase the response of the tumour to the next line of treatment, mainly chemotherapy. Based on these data, the concept of chemoimmunotherapy is proposed, which states that a judicious combination of immunotherapy with other cancer treatment approaches is necessary to achieve significant and long-term cancer control.
Passive immunotherapy, such as CIK, combines well with active immunotherapy, such as DCV, which mobilizes the patient’s immune system. Such a combination has the advantages of the immediate effect of the passive therapeutic side and the long-term effect that develops during the active immunotherapeutic side. Immunotherapies with CIK and DCVs are an advanced combination therapy since they work on several different principles, contributing to a broad, complex immune response against cancer. EXOSOMS can be administered in the form of a short i.v. infusion or as an injection. These are microvesicles with anti-tumour and regenerative potential, proven in vitro and in vivo studies as an additive to potentiate DCV and CIK.
• immunotherapy with DCV and CIK is not yet a standard cancer
treatment, but it can be used as an
additional advanced therapy
• immunotherapy with DCV and CIK
can be used as adjuvant or palliative
treatment of various malignant
diseases
• immunotherapy with DCV and CIK
is a personalized cancer therapy, the
applicability of which to an
individual patient is determined by
various factors, including:
– general health condition and
concomitant diseases of the patient
– stage of cancer
– standard treatment strategy
• immunotherapy with DCV and CIK
can be combined with chemotherapy,
hormone therapy, targeted therapy,
radiotherapy or other
immunotherapy methods
• DCV and CIK immunotherapy is
applied by a multidisciplinary team
of oncologists and immunologists,
together with standard treatment or
after its completion.
