Tumors

What is cancer fundamentally characterized by?

Uncontrolled cell division, often due to mutations in proto-oncogenes, tumor suppressors, or DNA repair genes.

What are the three types of cancer origins?

1. Spontaneous (e.g., leukemias)

2. Solid tumors

3. Virus-associated (e.g., HPV, Hepatitis B)

How can tumor antigens arise?

Tumor cells often express mutated self-proteins or viral proteins, making them look foreign to the immune system.

How can tumors evade CTL detection?

1. Downregulate MHC I

2. Present mutated peptides poorly bound to MHC I

3. Express inhibitory ligands like PD-L1

What is PD-L1 and how does it affect CTLs?

PD-L1 is an inhibitory molecule on tumor cells that binds PD-1 on CTLs, suppressing their activity.

What is the goal of cancer immunotherapy?

To boost or direct immune responses (especially T cells) to effectively recognize and kill tumor cells.

Why is cancer immunotherapy challenging for solid tumors?

Because tumor-specific immune activation is often weak or absent in vivo due to poor antigen presentation and immune suppression.

What are Tumor-Infiltrating Lymphocytes (TILs)?

T cells that have already infiltrated the tumor and are likely to recognize tumor antigens.

What makes TIL therapy effective?

TILs are selected for high-affinity recognition, and no need to identify the tumor antigen beforehand.

What are the three components of a CAR?

1. Antibody domain (single chain variable fragment)

2. CD3 signaling domain

3. CD28 co-stimulatory domain

How is CAR-T different from normal TCRs?

CARs recognize antigen directly, without MHC presentation, and bypass normal co-stimulation requirements.

What cancers has CAR-T therapy been most successful for?

Blood cancers, like B-cell leukemias and lymphomas.

What risk is associated with CAR-T therapy?

Autoimmunity, especially if the target antigen is also expressed on essential normal cells.

What are monoclonal antibodies (mAbs)?

Identical antibodies derived from a single hybridoma clone, engineered to target specific tumor antigens.

How are hybridomas created?

By fusing plasma cells (produce specific antibody) with myeloma cells (immortal but non-productive).

What is the mechanism of action of monoclonal antibodies in cancer therapy?

They bind tumor antigens, leading to ADCC or blocking essential signaling pathways.

What immune checkpoint molecules are targeted in cancer therapy?

PD-1/PD-L1 and CTLA-4

How does PD-1 blockade work in cancer therapy?

Blocking PD-1 or PD-L1 prevents tumor-induced CTL suppression, allowing T cells to kill tumor cells.

How does CTLA-4 blockade help in cancer therapy?

Prevents CTLA-4–mediated T cell anergy, restoring T cell activity against tumors.

How do mRNA cancer vaccines work?

Inject mRNA encoding tumor antigens, which is taken up by APCs to generate MHC I (CTL) and MHC II (Th) responses.

3 major components of CAR(chimeric antigen receptor)

• Extracellular single heavy/light chain antibody for antigen recognition

• Intracellular domain contains CD3 for signaling

• Intracellular domain contains CD28 for co-stimulation