Use of immunology to distinguish cancer cells and cancel metabolism Flashcards
Carcinoembryonic Antigen (CEA) is:
a) A tumour-specific marker found in 70% of all human cancers
b) A tumour-associated marker found in 70% of all human cancers
c) Used as a screening test for all solid tumors
d) It is the target of the screening test for colorectal cancer
b) Tumour-associated marker found in 70% of all human cancer
Provenge is:
a) a type of humoral antibody
b) a type of cellular immunotherapy
c) a checkpoint inhibitor for prostate cancer
d) a type of cytokine therapy
e) none of the above
b) a type of cellular immunotherapy
Which one of the following statements about checkpoint inhibitor blockade is true:
a) If there is an ongoing host immune response against tumour specific antigens checkpoint
inhibition blockade is not a viable therapeutic option.
b) If there is an ongoing host immune response against tumour specific antigens checkpoint inhibition blockade is considered as a therapeutic option for some cancers.
c) Ipilimumab blocks PD-1 signaling in T cells
d) CTLA4 binds CD28
b) If there is an ongoing host immune response against tumour specific antigens checkpoint inhibition blockade is considered as a therapeutic option for some cancers.
Immunosurveillance is the immune …of the patient in cancer …, …, …, and dissemination
status of the patient in cancer initiation, promotion, growth and dissemination
Tumor immunology is the use of immunologic technology to…. in order to diagnose, localize, treat and follow the progress of tumour growth and remission
a. …
b…
detect tumour markers
a. tumour specific
b. tumour associated
what are inbred mice (syngeneic)
Theyre mice strain with identical genetics and will take grafts from each other without rejection because the immune system doesnt recognize those tissues as foreign, and dont reject them
What are TSTA’s (Tumour specific transplantation antigens)
Theyre like flags found on cancer cells. They signal the immune system to attack these cells.
They took one cured mice from cancer, and 100 brothers and sisters, and exposed the tumor back again to the mice and his siblings. During the first exposure to the tumor, before ressection (surgery), the mouse developed … to the tumor tissue. The others had a typical tumor reponse rejection. What did the tumor develop in the first mice?
an immune response
The tumor developed a tumor specific antigen (TSTA)
What does Putative mean
Presume, supposed, assumed, presumed
Immunotherapy 0 - What’s Coley’s Toxin? Its a ….that he injected directly into tumors of patients with head and neck cancer.
Its a mixture of attenuated bacteria that he injected directly into tumors of patients with head and neck cancer.
What is the result of the Coley’s Toxin?
In a significant number of cases, there was a regression of the tumor
Immunotherapy I - Cell based therapies: Vaccines: exposure of patient’s own … or … to her tumor cells after removal of that tumour surgery. The tumor cells were then reinfused into the patient, often with… of the tumor. This therapy is approved, and called …
Exposure of patient’s own lymphocytes or dendritic cells to her tumor cells and removal of that tumor surgery. The tumor cells were then reinfused into the patient, often with regression of the tumor. Called Dendreon Provenge
Whats Dondreon’s provenge
its used for advanced prostate cancer, they train immune cells outside the body to recognize and attack prostate cancer cells before being reintroduced into the patient like a vaccine
Immunotherapy II - Humoral antibodies: Study of monoclonal antibodies by Kohler and Milstein. They target particular cells or proteins, they can trigger …or block…that promote disease, aiding in treatments for conditions like cancer or autoimmune disorders
immune response or block signal that promote disease
Whats Herceptin used for and whats the type of immunotherapy?
Is humoral antibodies, more specifically monoclonal antibody therapies, used in HER2-positive breast cancers and other tumors as well.
What’s Rituximab ; role and disease
Its a monoclonal anti-B (CD20) lymphocyte antibody, used with significant sucdess in B-cell leukemias and lymphomas
Immunotherapy III : Pro-inflammatory cytokines help the grow the body’s own soliders, called the… which may naturally fight against cancer
T lymphocyte populations
What are their role and link to Pro-inflammatory cytokines? : Interferon alpha, tumour necrosis factor and interleukin-2 (IL-2)
INF-alpha helps fight cancers
TNF can shrink tumors
IL-2 boosts T cells
What does the in vitro approach avoid in pro-inflammatory cytokines?
in vitro approach helps avoid the substantial side effects observed in living systems during cytokine therapy by growing potential anti-tumor T cells outside the body, which are later reintroduced into the patient.
Immunotherapy IV: Checkpoint inhibitor blockade has revealed that a particular immune response, once activated, effectively stops the progression of the immune response itself.”
Give two examples of molecules that interfere with the activation linkage that occurs between dendritic cells and CD4-positive helper T (Th) cells that initiate immune reactivity.
CTLA4 and PD1
What happens if you use monoclonal antibodies againt CTLA4 and PD1?
The anti-tumor immune response is allowed to go forward without inhibition (ITS GOOD, we want anti-CTLA4 and anti-PD1)
True or false: MHC-peptides do not work without costimulation to B7-CD28
True, the activation of T cells through the Major histocompatibility complex (MHC) presenting antigens requires a second signal known as costimulation, which often involves the interaction between B7 and CD28
We knows that the costimulation of B7 and CD28, theres a release of cytokines, that results on an ungoing toxix immune response for cancer… but what happens if the costimulation of CTLA4 or B7 is blocked?
There no T-cell activation and you need to add an anti-CTLA4 or anti-B7 to restart the system again and then theres release of cytokines, and let the anti-tumor response go forward.
What are Bispecific T-Cell engagers, example with CD3 and CEA, its linked by?
Bispecific T cell engagers, with CD3 and CEA are designed to connect two types of cells (T cells and cancer cells)… BITES are like bridge, linking T cells (CD3) directly to cancer cells (CEA). Linked by a short peptide chain… and Tcell attacks and kills cancer cells
Im a protein found on the surface of T cells (a type of immune cell) in the Bispecific T cell Engagers
CD3
Im a protein found on certain cancer cells, (antigen) that binds to CD3 to kill the cancer cells
CEA (carcinoembryogenic Antigen)
Whats a Car-T cell? function?
Chimeric Antigen receptor T cell, and its a type of immunotherapy that modifies a patients T cells in a lab. They engineer the T cells to expres a chimeric antigen receptor (CAR) on their surface. once the T cells are able to recognize specific antigens found on cancer, theyre re-infused into the patient and they destruct the tumor
PVS-RIPO has been shown to infect glioblastoma tumours through … signaling the immune system to destroy the tumour
CD155/Necl5 binding
Out of place : Which syndromes, involving the presence of hormones that shouldn’t be there, are associated with paraneoplastic syndrome?
Paraneoplastic syndromes can involve the presence of hormones such as ACTH and ADH that are normally associated with the affected tissues
Out of place: What chromosomal translocation leads to the formation of the philadelphia chromosome and is associated with chronic myeloid leukemia
BRC-ABLC translocation between 9 and 22 create philadelphia chrosome, which can be targeted by drugs like Gleevec
Out of whack: What abnormal protein is commonly found in multiple myeloma and leads to the M spide seen in electrophoresis?
The overproduction of immunoglobulins by malignant plasma cells result in the M peak, often detected in multiple myeloma, and is assoiated with Bence-Jones proteinuria
Out of time: Which type of antigens, commonly associated with cancers, are indivative of oncofetal antigens that disappear in adult life but reappear with cancer
Oncofetal antigens such as CEA (carcinoembryogenesis antigen) and AFP (alpha-Fetalprotein) are markers that disappear after birth but can reappear in cancerous conditions
What are the various applications of tumor markers in the context of cancer management?
Detection, diagnosis, monitoring treatment reponse, predicting prognosis, determining cancer stage, etc..
what was a significant limitation in early immunologic studies concerning tumor antigens
Lack of adequate control tissue made it difficult to distinguish tumor-specific antigens from individual-specific antigens (alloantigens)
What was a restricted approach in producing antitumor antisera in early studies
The production of antitumor antisera primarily relied on a single technique, antiserum absorption
How many procedure we commonly utilized in early immunologix studies
Only one or two procedure were often employed, limiting the range analysis
How was the deficiency of inadequate control tissue addressed in studies of colorectal cancer
The study focused on colorectal cancers obtaining both tumor and normal tissue from the same patient, allowing a direct comparison
What approach was adopted to overcome the limited production of antitumor antisera
Antitumor antisera were produced using both immunologic tolerance and absorption techniques, broadening the scope of antibodies generated
How was the limitation of using only a dew procedures addressed in later studies
Later studies employed multiple procedures allowing for a more comprehensive analysis of tumor antigens and their immune reponse
In an experiment regarding immunologic tolerance what was observed in mice concerning graft rejection
Mice rejected grafts from each other, indicating a lack of tolerance between their immune system
How did scientists induce immunologic tolerance in newborn rabbits?
Scientists induced imunological tolerance in newborn rabbits by exposing them to a normal human bowel
What was the aim of injecting tumor tissue from the same patients into the grown-up rabbits
When the rabbits matures, scientists injected tumor tissue from the same patients, hoping that the rabbits would react only to the tumor tissue, not the onrmal tissue, due to the induced immunological tolerance
What was the process involved in the absorption technique for producing antitumor antisera
The absoption technique involved injecting a male rabbit, bleeding the rabbit and then adding excess human tissue from the same patient to the blood sample
What was the purpose of adding excess human tissue to the rabbit’s blood sample in the absorption technique
The excess human tissue was added to reduce the antibodies against non-tumor components, aiming to focus the antibodies specifically against the tumor antigens in the blood sample
How were tissue samples analyzed to evaluate the antigen in question
over 5000 tissues from normal, inflammatory and cancerous tissues obtained from operating rooms, labs, were assessed using precipitin-inhibition techniques
Which specific cancers tested positive for the antigen in the tissue analyses
Only primary cancers originating from lowe 1/3 of the esophagus to the anorectal junctions, along with primary hepatomas and pancreatic cancers, showed a positive presence of the antigen
Which tupes of cancers including metastases, tested negative for the antigen in the tissue analyses
Cancer from organs other than the specified GI tract locations, even metastatic cancers originating from GI tissues (sucha s hepatic metastases from lung or breast
Where is the same band/antigen found during fetal and embryonic development
The same band/antigen is present in the fetal gut, pancreas, and liver during the first two trimesters of gestation even in spontaneous abortuses
What antigen was discovered in these fetal and embryonic GI organs
Carcinoembryonic antigen (CEA) was found
Why did the discovery of CEA face challenges and skepticism
Data from tumor biology often lacks reproducibility, and the discovery of CEA in these organs was initially met with silence due to the rarity of reproducible findings in tumor biology
what changes were observed in colonic carcinomas concerning CEA expression and tissue structure?
In colonic carcinomas, there was a loss of polarized CEA expression and a disruption of normal tissue architecture
What is the nominal molecular mass of CEA
CEA has a nominal mass of 180 kd, with over 50% of this mass attributed to carbohydrate side chain and 28 potential N-linked glycosylation site
How many CEA-related antigens were tested using monoclonal antibody technique
9 CEA related antigens
What consensus was reached regarding the epitopes of CEA
A consensus conference identified nine mahor epitopes of either peptide or glycopeptide structure, highlinghting that CEA is part of the CEACAM family of molecules
What is the nature of CEA in termes of its membrane structure
CEA is a membrane glycoprotein, probably membrane anchored rather than transmembrane in nature
how many members make up the CEA gene family and where are they located?
CEA gene family has 29 membrers, which 18 being active genes and 11 being pseudogenes, situated in two clusters at chromosome 19q13.1
What are the possible functions of CEA
intercellular adhesion,
Adhesion between bowel mucus and bacterial cell surface
involvement in stem cell maturation
What do many of the 18 active genes in the CEA family code for?
adhesion molecules known as CEACAMs which serve various functions in different areas such as cancer development, apoptosis, neogenesis, metastasis, insulin metabolism
Why cant tumor markers, like CEA, be used for screening purposes
Tumor markers due to their small amounts in blood, are inadequate for screening purposes
What signidicance does CEA level. of 5ng hold
If CEA leverls rise above 5ng, it typically indicates a cancerous conditions
How can CEA aid in post-operative patient monitoring?
Monitoring CEA level post-surgery helps determine if a tumor is recurring, assisting in patient follow up
Why is CEA considered tumor-associated rather than definitive cancer marker
CEA is found in small amounts in normal tissues making it tumor-associated rather than specific cancer marker
Why isnt CEA suitable as a screening test despite its elevation in certain conditions
Elevated but stable blood levels of CEA can be found in various inflammatory states, endering it unsuitable for screening
Apart from GI cancer, where else might elevated and rising CEA levels be detexted
Rising CEA levels are not exclusive to GI cancers : They may be found in approximately 70% of all human cancer
What are the monitoring guidelines from ASCO for patients with Dukes II and III stages of colorectal cancer after surgery or chemotherapy
ASCO recommends quaterly monitoring for three yeards to guide post-treatment care
How does the National comprehensive cancer network suggest utilizing CEA testing for patients with T2 or higher disease?
The NCCN recommends serial testing for 5 years, especially for those potentially undergoing resection of isolated metastases. Pre-poerative CEA levels predict disease-free intervals, and CEA decline post-op guides adjuvant therapies
What role does CEA play according to the American Joint Commission on Cancer, WHO, and Pathology & Genetic of Tumors of Digestive System?
CEA serves as an independent prognostic factor, aids in TNM classification, and helps diagnose recurrence or successful tumor resections
What therapeutic approached target CEA
Radioactive monoclonal anti-CEA therapy,
Pentacea for lung cancer
Vaccinia virus/Fowlpox-CEA/MUC1 immunization, and anti-CEA antibody directed enzyme producing therapy
What significant observation was made on the 50th anniversary of CEA
Despite its 50 year history, the lack of alternative miomarkers leaves CEA still relevant, despite exptectations for its obsolescence.
