cell based therapeutic Flashcards
objectives
. to be able to describe what a cell therapy is and give examples (DCs, T cells, NK cells, γδΤcells).
.To know what adoptive cell therapy means.
what is the goal
General ideas are taken up in the exam and the goal for this lecture is
to explain concepts of therapies and their properties. Not too detailed.
what is cellular therapy
is the stimulation of body’s cells to fight the diseases with focus on immune cells therapy
where does this therapy applicable
cancer, autoimmunity, infection (HIV), allogeneic transplantation.
What are the type of cell therapy
- non-engineered immune cell therapy: adoptive cell therapy
- engineered immune cell therapy: immune cells isolated, genetically modified or expansion
what is the adoptive cell therapies
using a patient’s immune cells to fight off diseases
Dendritic cell-based immunotherapy
. Know what a DC is and its role in immunity.
*Be able to describe the three main treatment modalities targeting DCs (in vivo activation, in vivo expansion, blocking of inhibitory signals). Give examples of each.
what are DC
-bridge adaptive and innate immunity
-professional antigen presenting cell
- T cells responses are initiated by the DC
what does DC involve in as APC
- Ag processing (process of displaying pathogen on the cell surface)
-Ag presenting (when APC display the pathogen in the way T cells can see it )
what are the treatment used in DC therapy
- in solid tumour: is able to migrate in the lymph node and transport tumour antigen then present it to T cell which initiate T cells activation
is DC required for T cells immune therapy
yes
what are the 2 functional classes of DC immune therapy
- plasmacytoid Dc (pDC): express CD123, involves in sensing viral infection and production of large amount of interferons
- conventional DC (cDC): express CD11c, activator of naive T cells and type1, cDC1 involve in activation of CD8+ T cells
why is it so hard to cure solid cancer
because of tumour microenvironment which is immunosuppression that give it the ability to avoid immune cells recognition and killings
why is DC therapy used in solid tumour treatment
because
- cDC1 interact with various immune cells like NK, T, and macrophage though cytokine and chemokine
- cCD1 has the capacity to present the Ag to the CD8+ T cells and activate T cells ex vivo
what are the treatment that target DCs
- in vivo activation: this involve stimulating existing DC within the body and enhance their ability to present antigens and activate T cells. by using various agent like cytokines, toll-like receptor agonist, DC response can be improved leading to robust of immune response against tumour cells.
- in vivo expansion: involve increasing the amount of DC present in tumour microenvironment particularly cDC1s which initiate anti- tumour T cells immunity. this method aim to restore DC function that maybe in dysfunctional in the TME leading to enhance/improvement of immune response.
- block inhibitor signal: tumour often employ various mechanism to suppress immune response so by inhibiting those signal it is possible to enhance the activity of the DC and improve the anti-tumour response.
- Dendritic cell vaccines: is not yet used but is showing promising in future. this is done by isolating immature DC from the patient and generate immature DC with GMC and IL-4 to give maturation, then activate DC in presence of tumour fragment and then re- infuse mature tumour specific DC.
what are the drawback of the above treatment method that target DC
single agent administration in patient. so, is not effective.
means is not combined with other therapies.
2) γδ Τ cells
*Know what a γδ Τ cell is and its role in healthy individuals compared to cancer patients.
*Be able to describe different ways that γδΤ cells can be exploited for therapies. Focus mainly on DOT cells (for this lecture).
what are γδ Τ cells
are subset of T cells having γδ heterodimer as a Τ cell receptor.
is between innate and adaptive immunity
where are γδ Τ cells highly found
gut mucosa
what is γδ Τ cells role in infection
-act as first line of defence
- able to create immunological memory
what does γδ Τ cells ability in cancer cells
γδ ΤCR can recognize more than one ligands on the tumour target
what is the different of γδ Τ cells in healthy and cancer individual
- role in healthy person: they generally produce anti-tumour cytokines and attack tumour cells cytotoxically.
- role in cancer patients: they are inactivated or deleted because they can lead to tumour progression by expression of IL-17. and it increase expression of myeloid derived suppressor cells (MDSCs) in TME.
what is tolerogenic profile
involves in secretion of cytokines likeIL-10 and IL-17 which promote immune regulation and enhance inhibitory checkpoints molecule expression in local microenvironment.
how can you use Therapeutic concepts of γδ T cells
you can use in vivo stimulation method followed by adoptive cell transfer
what is the Therapeutic concepts of γδ T cells
- delta one cells (DOT cells): enhance NK cells response.
drawback: downregulation of natural activity. - CAR γδ T cells: carrier of chimeric antigen receptors, engineered antigen receptor for tumour specific antigen.
drawback: control by cytotoxic receptor - TEG: target cancer by combining receptor expressed on gama - delta T cells with highly proliferred and memory capacity of alpha - beta T cells
3) Natural Killer (NK) cells
*Know what a NK is and its biological role.
*Be able to describe the three main treatment modalities targeting NKs (cytokine supplements, monoclonal antibodies, adoptive cell therapy). Give examples of each.
what is NK cells
are innate immune system cells that doesn’t carry Ag specific receptor like Ab or TCR
how does NK be activated
- via receptors because it doesn’t have Ag specific receptor
- via ADCC
how does NK works
by releasing cytotoxicity
how does NK therapeutic target cancer
the possible target is to enhance NK cells function and cytotoxicity
how can we enhance NK cells function and cytotoxicity
- cytokine supplement like IL-5 (expand NK cells and promote their cytotoxic activity)
2.monoclonal antibody:
3. adoptive cell therapy: by antibody engineering which enhancing NK ADCC response to tumour cells with specialized antibody. this we use allogeneic
4) T cells
For Τcells;
*Understand the difference of engineered vs non-engineered T cell therapies.
*Be able to describe the three main non-engineered treatment modalities targeting T cells (TILs, viral-specific CTLs, Treg cells). Give examples of each.
what is the difference between engineered vs non-engineered T cell therapies
- engineered T cell therapies: refers to the genetic modification of T cells to enhance their anti-tumour activity.
- non-engineered T cell therapies: refer to the utilize of body’s own T cells to enhance their anti-tumour activity.
describe the three main non-engineered treatment modalities targeting T cells
- TILS: they infiltrate the tumour tissue as part of immune response. they attack and recognize tumour specific antigen but their activity can be suppressed within TME.
Therapeutic Approach: they are isolated form the patient’s tumour, expanded ex vivo using IL-2 and re-infused into the patient to boost their anti-tumour activity. - CTLs: are T cells that are specifically activated to recognize and kill cells that are infected with virus, in context of cancer, they can target tumour cells that express the viral antigen presented by MHC class I molecule.
Therapeutic Approach: they are isolated form the patient’s blood and they are expanded in vitro in case of EBV they are infused back into the patients to target and eliminate tumour cells.
drawback: rejection of allogeneic cell product during transplant - Treg cells: has mediate effect of producing immunosuppressive cytokines.
Therapeutic Approach: they are isolated in the patient are are expanded to enhance their function. in cancer, they are used to modulate immune response either by enhancing anti-tumour immunity or preventing excessive activation of immune cells that can lead to autoimmunity.
what makes cellular therapy successful
safety
efficacy
manufacturing consideration
what are the challenges
differentiation
design
and delivery
what is Cell source: allogeneic (donor), autologous (self)
allogeneic (donor), cells that are generated form the donor
autologous (self) cells that are generated form within the own body
