Hi rdrokit I noticed that you were doing a course on Immunotherapy - how was it ?
Some links from the Scancell (cancer vaccines) site are below and I wonder if it may be of interest to you and others.
http://www.scancell.co.uk/products/product-pipeline
Great course. I learned a lot about the immune system and immunology. Below are a few notes I made throughout the course.
Myeloid stem cell - produce red blood cells
Lymphoid stem cells - produce B cells & T cells.
Monocyte - largest of white blood cells. When they leave blood stream they become macrophages and found in lungs, skin and gut. Follow pathogens and destroy them with their granules.
Neutrophil - another type of white blood cell that are in high numbers in the blood stream. They use their toxic granules to destroy bacteria.
NK cells (natural killer) - react quickly -
The dendritic cell is really important for communication between white blood cells. The dendritic cells travel to lymph nodes to stimulate immune cells that are able to recognize the invading pathogen.
In the lymph nodes, T cells use their receptor to scan the dendritic cells for any pieces of foreign proteins displayed by their MHC molecules. The dendritic cells then activate the T cells and give them information on how to find the pathogens.
Helper T cells' main role is coordinating immune response, giving instructions to other types of immune cells.
The main job of cytotoxic T cells is to seek out infected cells displaying the same foreign protein on their MHC molecules and to kill them.
The other type of lymphocytes, B cells, also have specialized receptors on their surface, this time called B cell receptors. Ultimately, B cells that recognize foreign proteins or pathogens, such as bacteria, start making these in a form that can be released from the cell. These are called antibodies, and they can stick to the invading pathogens, stopping them in their tracks and marking them for destruction. B cells can also make antibodies that can stick to infected cells.
Cancer is caused by our own body's cells multiplying out of control. Cancer cells contain changes to their genetic code, their DNA, compared to normal cells. In other words, mutations-- making them subtly, but importantly, different. The fact that cancer cells are often self-sufficient in terms of growth signals, explaining how they grow outside of the normal controls. The fact that unlike normal cells, cancer cells can multiply indefinitely without stopping. They are essentially immortal.
Immunosuppression - Research has shown that transplant recipients are at increased risk of a large number of different cancers. Some of these cancers can be caused by infectious agents, whereas others are not. The four most common cancers among transplant recipients and that occur more commonly in these individuals than in the general population are non-Hodgkin lymphoma (NHL) and cancers of the lung, kidney, and liver. NHL can be caused by Epstein-Barr virus (EBV) infection, and liver cancer by chronic infection with the hepatitis B (HBV) and hepatitis C (HCV) viruses. Lung and kidney cancers are not generally thought to be associated with infection. People with HIV/AIDS also have increased risks of cancers that are caused by infectious agents, including EBV; human herpesvirus 8, or Kaposi sarcoma-associated virus; HBV and HCV, which cause liver cancer; and human papillomavirus, which causes cervical, anal, oropharyngeal, and other cancers. HIV infection is also associated with increased risks of cancers that are not thought to be caused by infectious agents, such as lung cancer.
Graft versus tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T lymphocytes that are beneficial for recipient. Donor T-cells eliminate malignant residual host T-cells (graft versus leukemia) or eliminates diverse kinds of tumors.[1] GvT might develop after recognizing tumor-specific or recipient-specific alloantigens.[99] It could lead to remission or immune control of hematologic malignancies.[2] This effect applies in myeloma and lymphoid leukemias, lymphoma, multiple myeloma and possibly breast cancer.[3] It is closely linked with graft versus host disease phenoma (GvHD). CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect.[4] The biology of GvT response still isn’t fully understood but it is probable that the reaction with polymorphic minor histocompatibility antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is involved.[5][6] This response is mediated largely by cytotoxic T lymphocytes (CTL) but it can be employed by natural killers (NK cells) as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT.
The abscopal effect is a phenomenon in the treatment of metastatic cancer where localized treatment of a tumor causes not only a shrinking of the treated tumor but also a shrinking of tumors in different compartments from the treated tumor. Initially associated with single-tumor, localized radiation therapy, the term has also come to encompass other types of localized treatments such as electroporation and intra-tumoral injection of therapeutics. While this phenomenon is extremely rare, its effect on the cancer can be stunning, leading to the disappearance of malignant growths throughout the entire body. Such success has been described for a variety of cancers, including melanoma, cutaneous lymphomas, and kidney cancer.
Scientists are not certain how the abscopal effect works to eliminate cancer in patients. Studies in mice suggest that the effect may depend upon activation of the immune system. In a case study reported at Memorial Sloan-Kettering Cancer Center in New York City,[1] changes in a metastatic melanoma patient’s immune system were measured over the course of treatment. The team observed changes in tumor-directed antibody levels and immune cell populations that occurred at the time of the abscopal effect. These findings support the idea that a localized treatment may broadly stimulate the immune system to fight cancer. At this time, various immune system cells, including T-cells and dendritic cells, are believed to play a primary role.
Effects in tissues adjacent to the irradiated area are bystander effects and are not necessarily mediated by the same mechanisms as abscopal effects.
This strong immune response against a tumor even has a name-- the graft versus leukaemia effect. In rare cases, it has been reported that infection can lead to regression of cancer. Early clinicians attempted to treat tumors by injecting a combination of bacteria into them, and it was thought that the body's increased response to the bacteria also helped to fight the cancer. And today, injection of the BCG vaccine, which is usually used to vaccinate people against tuberculosis, into the bladder is used as a treatment for bladder cancer. It's still not entirely clear how this treatment works, but it seems to encourage the immune activation in the lining of the bladder, which helps to kill off the cancer cells.
Immune cells are able to migrate out of the blood and crawl through the tissues of the body ready to fight disease. And, in some cancers, it's been observed that, the more immune cells there are in the tumor, the slower the patient's cancer progresses. In fact, in some cases, the immune signature inside the tumor might be an even better indicator of how the disease will progress than traditional methods used for staging cancer. On top of this, there is a lot of evidence showing immune cell recognition of cancer cells in the laboratory, and this gives scientists much hope for the future of immunotherapy development.
So assuming the immune system does play a role in combating cancer, how then do tumour cells avoid being attacked?
Firstly, whereas infected cells can look quite different to the immune system from normal cells, often the changes in cancer cells are quite subtle so they can look pretty similar to the immune system. This means that in many cases they are inherently disguised. Despite this, by inspecting target cells closely, immune cells can potentially recognize and destroy cancer cells. However, cancer cells have a number of tactics they use to evade an immune cell poised to attack. Here, we will show you three tricks.
Firstly, cancer of cells can send direct messages in the form of small proteins called cytokines that tell the immune cells to ignore the cancer cell.
Secondly, T cells rely on special cellular MHC molecules that display bits of proteins that are located inside the cancer cell for recognition. If tumor cells lose these systems of surveillance, it effectively means they can escape close inspection.
Thirdly, cancer cells can exploit the fact that our immune cells have emergency off switches on their surface to prevent them going out of control. By pressing these off switches, cancer cells can turn off our immune cells when they are poised to attack. Finally, it's useful to think about cancer as evolving like in Darwinian evolution. Cancer cells can mutate and change over time, creating a diverse population of cells. The cancer cells that's are most adept at survival and about suppressing the immune system are the most likely to come to dominate the population. Understanding how this occurs is crucial if we are to develop novel approaches to cancer treatment.
Immunotherapy is an umbrella term that is applied to several different types of treatments, but each has the common aim to use the immune system to kill cancer cells. This might either involve rear whitening natural anti-tumor t-cells while boosting their numbers in the body or giving patients t-cells that have been reprogrammed to recognize cancer. These multiple strategies are necessary because there are so many different types of cancer, more than 200.
Understanding the immune signature inside a patient's tumor is critical if we are to develop new immunotherapy's for cancer. Immunohistochemistry, or IHC for short. And it's quite commonly used in the diagnosis to assess whether a patient is suitable for a drug therapy. Also used to examine the immune signature inside a tumor.
There are a number of B-cell tumors. So in adults, chronic lymphocytic leukaemia is the commonest leukaemia in adults. And it's usually a very slow and indolent leukaemia, which is treatable. But unfortunately, it's not curable. So there is an unmet need for those patients. In children, the commonest leukaemia is acute lymphoblastic leukaemia. And most children are cured with that leukaemia. But there are probably about 10% of children where, unfortunately, their disease hasn't been able to be cured. There are a number of other B-cell malignancies. You can get acute lymphoblastic leukaemia in adults, where the prognosis is actually quite poor. And then, most non-Hodgkin's lymphomas are B cell in origin.
Artificial T cell receptors (also known as chimeric T cell receptors, chimeric immunoreceptors, chimeric antigen receptors (CARs)) are engineered receptors, which graft an arbitrary specificity onto an immune effector cell. Typically, these receptors are used to graft the specificity of a monoclonal antibody onto a T cell; with transfer of their coding sequence facilitated by retroviral vectors. The receptors are called chimeric because they are composed of parts from different sources.
Chimeric antigen receptor (CAR) Artificial T cell receptors are under investigation as a therapy for cancer, using a technique called adoptive cell transfer.[1] T cells are removed from a patient and modified so that they express receptors specific to the particular form of cancer. The T cells, which can then recognize and kill the cancer cells, are reintroduced into the patient. Modification of T-cells sourced from donors other than the patient are also under investigation.
As you've heard previously, T cells carry a T cell receptor that enables them to recognize fragments of proteins. And some of these can recognize proteins expressed on cancer. However, sadly, in many cancer patients, such T cells a too few in number, and can't function very well, so they're unable to control the tumor. Therefore, one approach to treat these patients is to use genetic engineering to reprogram large numbers of their T cells, so that many more of them can now recognize and destroy the cancer. We can do this reprogramming of T cells in two different ways.
One approach is to introduce a gene that encodes a new T cell receptor, one that can recognize a protein on the cancer cell. The other approach is to introduce a gene that encodes what we call a chimeric antigen receptor, or CAR. A CAR is a fusion between an antibody that recognises cancer cells, and the signalling component of the T cell receptor. So when a T cell engineered to express such a CAR encounters a cancer cell, the antibody component binds to the cancer, and this will then deliver a signal to the T cell, causing it to kill that cancer cell. Key to the success of using these engineered T cells is the selection of an appropriate target protein.
Vaccines are one of the single greatest medical advances ever made, and have had a truly dramatic impact on human health. For many years now, immunologists have been trying to see if vaccines can be used to fight cancer. There are already some vaccines being used to prevent certain types of cancer from developing. One example is the human papilloma virus vaccine that is now being given to young women in many countries. This vaccine works by preventing infection with certain strains of papilloma virus that are associated with cervical cancer. We're already seeing good size of protection from cervical warts that these viruses can also cause. We hope to see that this protection extends to cancer, as well, in the future.