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Dosage II > Cell-Based Therapuetics 1 > Flashcards

Cell-Based Therapuetics 1 Flashcards

1
Q

Biotherapuetics

A

-living drugs
-larger
-molecular specificities against the target
-activity driven by structure and interaction w cells

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2
Q

Where do biotherapeutics go?

A

-DNA therapeutics go to nucleus
-protein therapeutics on membrane
-RNA therapuetics in cytoplasm
-cell-based outside of cell

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3
Q

Cell-based therapies

A

-gene therapy when it deilivers or is engineered w a gene
-non-modified cell therapy
-stem cell therapy
-cell-based vax

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4
Q

Gene therapy

A

-virus-delivered genes
-gene-edited cells

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5
Q

Cell therapies can contain

A

-genes and antibodies
-can start as a gene and grow into antibody
-ex vivo

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6
Q

Classes of cell-based therapies

A

-stem-cells and stem cell-derived
-immunotherapies

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7
Q

stem cells

A

-cell therapy
-does NOT involve immune cells

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8
Q

Immunotherapies

A

-involve immune cells
-cancer vax and cell-based immune therapies
-include native and cell-based gene therapies
-CAR-T and TILs and cancer vax

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9
Q

Gene therapy

A

-in vivo or ex vivo engineering
-treat gene defect

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10
Q

Ex vivo

A

-gene-therapy that is cell therapy

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11
Q

Casgevy

A

-ex vivo CRISPR/Cas9- cell therapy
-NEW! 2023 for sickle cell
-extract stem cells
-infuse CD34 cells w normal gene for hemoglobin
-put stem cells back in patient

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12
Q

FDA approved cell products

A

-stem cell (CD34 HSCs)
-TIL
-CAR-T (gene-based)
-CRISPR-edited CD34 HSC (gene-based)
-cancer vax

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13
Q

Stem cells

A

-totipotent (whole organism)
-pluripotent (all tissues)
-multipotent (specific cells)

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14
Q

Which type of stem cells are FDA approved

A

-multipotent
-fetal tissue, cord blood, adult stem cells

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15
Q

Sources of stem cells

A

-bone marrow H and M
-liposuction M
-cord blood H
-specific tissue M

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16
Q

use of stem cells in cell therapy

A

-replacement cell therapy (alzheimers, parkinson’s, diabetes, arthritis)
-adult stem cells less versatile than embryonic stem cells
-only 22 embryonic cells lines are eligible for federal funding
-NO FDA approved tissue-regenerative stem cells yet
-FDA has only approved stem cell therapy for cord blood transplantation

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17
Q

Types of cell therapies that are immunotherapies

A

-adoptive cell transfer (CAR-T, TILs, NK cells)
-cancer vax (dendritic cells)

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18
Q

Modification of immune cells

A

-DC can be vax or TILs
-NK for CAR-NK

19
Q

Tumor infiltrating lymphocytes (TIL)

A

-tumor infiltrating lymphocytes
-cells associated w tumor
-tx melanoma

20
Q

CAR-T or CAR-NK (chimeric antigen receptor)

A

-synthetic genetic construct targeting a tumor antigen
-CAR-macrophages underdevelopment
-tx blood disorders, cancer, sickle cell disease

21
Q

When can FDA regulate stem cell therapies

A

-when more than minimal manipulation and/or it has a systemic effect
-exempt if minimal manipulation and homologous use (taking cells in and out of pt in same procedure w/o altering them)

22
Q

Hematopoietic stem cell transplantation

A

-from bone marrow, cord, blood
-FDA regulated unless it meets exemptions

23
Q

Cell therapy for HIV

A

-CAR-T
-gene-edited stem cells

24
Q

cell therapy for covid

A

-cells can target SARS-COVID

25
Q

How can immune cells kill cancer cells?

A

-antibodies or engineered cells recognize tumor antigen

26
Q

NK cells

A

-attack pathogen by engineering receptors that can recognize antigens of certain cancers
-release cytotoxic stuff that kills target cell

27
Q

Immune response

A

-innnate (NK)
-adaptive (T and B)

28
Q

Who is cell-based immunotherapy for?

A

-pt w advanced cancers (stage 4)
-pt who have not responded to primary tx
-pt whose cancers returned and spread after initial tx

29
Q

Autologous vs allogeneic

A

-autologous: cells from own body
-allogeneic: cells from donor

30
Q

Cells sourced from peripheral blood

A

-autologous
-pt-specific
-10% NK/T cells

31
Q

Cells sourced from cord blood

A

-allogeneic
-can be cryopreserved
-30% NK/T cells

32
Q

Cells sourced from cell lines

A

-commercially available
-allogeneic
-not like human cells

33
Q

Cells sourced from induce pluripotent stem cells

A

-allogeneic thru gene editing
-cryopreserved
-off-the-shelf

34
Q

Donor matching

A

-sibling best
-matched unrelated worst
-haploidentical family

35
Q

Chimeric antigen receptors (CARs)

A

-engineered receptor expressed on surface of immune cell (like antibody) that recognizes target
-can target tumor specific or tumor associated antigens

36
Q

CAR signaling

A

-activation = signal to kill target
-co-stimulatory domain patheays 4-1BB, CD28, CD8

37
Q

principles of CAR-T

A

-cells removed, modified, expanded, put back in pt
-pt preconditioned w chemotherapy to restrain immune response

38
Q

Anatomy of cell-based therapy

A

-drug product: immune cell + gene)
-drug substance (engineered molecular component)

39
Q

CAR structure

A

-scFv recognizes tumor antigen
-hinge to anchor scFv
-sends signal down thru membrane to sotimulatory domain

40
Q

TIL therapy

A

-Lifileucel
-approved 2024
-for melanoma

41
Q

TIL principles

A

-isolate cells from excised tumor
-T cells w multiple TCR clonse
-memory T cells
-T cells that express chemolines
-low toxicity!
-tumor accessibility could be problem
-ability to recover limited number of functional TILs

42
Q

steps of TIL therapy

A
  1. take cells from tumor
  2. isolate TILs
  3. expansion
  4. back into pt
43
Q

steps of CAR-T therapy

A
  1. T cell from blood
  2. genetic mod w TCR or CAR
  3. expansion
  4. back to pt
44
Q

CAR vs TCR

A

-same thing just using TCR instead of CAR

Dosage II (20 decks)

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