WEEK 12 – Oncology x Molecular Pathology

Allogeneic

= Cells or tissues from a donor for use in a patient

• (Originating from a different individual of the same species)

Allo-SCT (Allogeneic Stem Cell Transplantation)

= Procedure where a patient receives HSCs from a donor to replace their own hematopoietic system

Acute Myeloid Leukemia (AML)

= Type of cancer of the blood/ bone marrow characterized by a block in differentiation and uncontrolled proliferation of primitive blast cells 

Antibody-mediated cellular cytotoxicity (ADCC)

= Immune mechanism where an effector cell (NK cell) lyses a target cell that has been marked by antibodies

Autologous

= using patient’s own cells which are modified and re-infused

• (Originating from the same individual)

B-cell maturation antigen (BCMA)

= Protein found on the surface of mature B-lymphocytes and plasma cells, making it a key target for therapies in Multiple Myeloma 

Bispecific Antibody (BsAb)

= Artificial antibody that can simultaneously bind to two different types of antigen 

• In T-cell redirecting therapies, one arm binds to a tumor antigen and the other binds to a T-cell surface molecule 

CAR-T cell (Chimeric Antigen Receptor T-cell)

= T-cell that has been genetically engineered to express a CAR, which allows it to recognize a specific antigen on tumor cells without HLA restriction and subsequently kill them 

CHIP (Clonal Hematopoiesis of Indeterminate Potential)

= Condition where a hematopoietic stem cell acquires a mutation, leading to clonal expansion of blood cells that share this mutation, which may precede the development of a hematological malignancy 

Clonal hematopoiesis

= Process where a single HSC and its progeny contribute a disproportionately large fraction of mature blood cells 

Cytokine Release Syndrome (CRS)

= Systemic inflammatory response that can be triggered by immunotherapies like CAR-T cells and bispecific antibodies, caused by a massive release of cytokines from activated immune cells 

Dendritic cell

= Specialized type of APC that is highly effective at priming T-cell responses 

• Used in vaccines to stimulate an anti-tumor immune response

Donor Lymphocyte Infusion (DLI)

= Infusion of lymphocytes from the original stem cell donor into a patient who has relapsed after an allogeneic stem cell transplant

• Intended to induce a Graft vs. Tumor effect

Flow Cytometry

= Laboratory method used to detect and measure physical/ chemical characteristics of a population of cells or particles

• Key tool for immunophenotyping and detecting MRD

Graft vs. Host disease (GvHD)

 = Complication of allogeneic transplantation where immune cells from the donor graft attack the recipient’s (host’s) healthy tissues 

Graft vs. Tumor (GvT)

 = Beneficial effect in allogeneic transplantation where immune cells from the donor graft recognize and attack the recipient’s tumor cells

• Or Graft vs. Leukemia (GvL) 

Hematopoiesis

= Formation of blood cellular components

• Originates from HSCs which self-renew and differentiate into all blood lineages

Hematopoietic Stem Cell

= Pluripotent stem cell found in the bone marrow that gives rise to all other blood cells

• Characterized by pluripotency (differentiate into all blood cells) and the ability to self-renew

Induced pluripotent stem cells (iPSC)

= Type of pluripotent stem cell that can be generated directly from adult cells, providing a potentially unlimited source for creating universal therapeutic lymphocytes 

Leukemia Associated ImmunoPhenotype (LAIP)

= Abnormal pattern of protein (marker) expression on the surface of leukemic cells that distinguishes them from normal HSCs, used to track MRD by flow cytometry 

Lymphodepletion

 = Preconditioning chemotherapy regimen given before adoptive T-cell therapy

Goals: To improve the efficacy of the infused T-cells by:

• Eliminating regulatory T-cells (that suppress immune responses)

• Creating a favourable environment for the expansion/ persistence of the newly infused therapeutic cells

Measurable Residual Disease (MRD)

= Small number of cancer cells that remain in the body during/ after treatment, detectable only by highly sensitive methods like flow cytometry or RT-PCR

• Strong predictor of relapse

Minor Histocompatibility Antigens (mHags)

= Small protein differences between donor and patient that can cause donor immune cells to attack either cancer cells (good) or normal tissues (bad), even when HLA matches (but peptide doesn’t match) 

• Can be targets for GvT and GvHD responses 

  • If mHags are expressed on cancer cells → Donor T cells attack tumor cells

  • If mHags are expressed on healthy organs → Donor T cells attack normal tissues

Multiple Myeloma (MM)

 = Cancer of plasma cells (a type of WBC that normally produces antibodies)

• Characterized by clonal plasma cells in the bone marrow, monoclonal protein in serum/ urine and end-organ damage

Myelodysplastic Syndromes (MDS)

= Group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells

• Often characterized by cytopenias and dysplasia

  • Cytopenia = lower-than-normal number of blood cells in your blood, leading to conditions like anemia (low red cells), leukopenia (low white cells), or thrombocytopenia (low platelets) 

  • Dysplasia = Abnormal growth or development of cells, tissues, or organs, characterized by disorganized cells that look different from normal cells

Regulatory T-cell (Treg)

= Specialized subpopulation of T-cells that act to suppress immune responses, thereby maintaining homeostasis and self-tolerance

• Prevent GvHD but may also inhibit GvT

TRUCKs (T-cell Redirected for Universal Cytokine Killing)

= Advanced CAR T-cell design where the cells are engineered to secrete a cytokine (e.g., IL-12) upon antigen recognition, which helps overcome the immunosuppressive TME

Tumor Infiltrating lymphocytes (TIL)

= A patient's own T-cells that have naturally penetrated a tumor

• These cells can be isolated from the tumor, expanded in a lab, and re-infused as a form of adoptive cell therapy

Vididencel (DCP-001)

= An allogeneic, off-the-shelf, leukemia-derived dendritic cell vaccine designed to stimulate the patient's immune system to fight residual AML cells, used as a maintenance therapy

• The ADVANCE II trial was designed to validate Vididencel as an AML maintenance therapy for 20 MRD-positive patients in complete remission who were not scheduled for hematopoietic stem cell transplantation (HSCT)