cancer immunotherapy

Question 1

example of a theranostic nanoparticle-based treatment

Answer 1

Lutetium-177 PSMA Therapy (Lu-PSMA)

Question 2

treatment for prostate cancer: ____

targeting agent = ___

Answer 2

targeted radiation to the cancer sites

proprietary peptide (Lutetium-177)

Question 3

___ is a type of protein found in the surface of a cell, it’s located on the prostate gland, some tumors, and normal tissues

Answer 3

PSMA (prostate-specific membrane antigen)

Question 4

in some prostate cancers, ___ is the second most upregulated gene product, with an ____ fold increase over levels in nancancerous prostate cells

Answer 4

PSMA
8-12

Question 5

the PSMA molecule is bound with ___, this is a radioactive substance that damages and destroys prostate cancer cells in a targeted way

positive results observed as well after ___

Answer 5

lutetium-177

metastasis

Question 6

Lutetium-177 is the theranostic agent in treating prostate cancer, 177Lu-trastuzumab induced cell death via:

Answer 6

DNA double strand breaks, which interferes with DNA expression –> caspase-3 apoptosis

combination of low energy beta emissions along with gamma emission for imaging makes half life of Lutetium-177 6.7 days

Question 7

encapsulation of Letetium-177 in liposomes has these 2 effects:

Answer 7

• prolonged circulation time
• enhanced imaging contrast

Question 8

2 components of cancer immunotherapy

Answer 8

nanomaterials targeting microenvironment for cancer immunotherapy

cancer vaccines

Question 9

____ have opened new avenues for cancer treatment by stimulating the host’s immune system and have attracted significant attention for cancer therapy

Answer 9

immunotherapeutic agents

Question 10

tumor microenvironment: ____ play an impt role in regulating tumor growth, invasion, and metastasis

they constitute ~ ___% of tumor mass

Answer 10

TAMs (tumor-associated macrophages)

50%

Question 11

name the 2 types of tumor-associated macrophages (TAMs)

Answer 11

M1 - polarized phenotype (pro-inflammatory and immunostimulatory)

M2 - polarize phenotype (immunosuppressive) –> M2 macrophages can suppress CD8+ T cells to support tumor survival

Question 12

tumors tend to have a higher population of ___ macrophages

Answer 12

M2

Question 13

upon initial exposure to antigen in the presence of polarizing cytokines, ___ cells can differentiate into a variety of different ___, each producing distinct ____ profiles

Answer 13

naive CD8+ T cells

Tc subsets

cytokine

Question 14

what are the 2 nanotechnology-based strategies to modulate macrophage functions?

Answer 14

1- depletion of M2-polarized macrophages

2- reprogramming of M2-polarized macrophages to M1-polarized macrophages

Question 15

depletion of M2-polarized macrophages:

___ has been reported to regulate the proliferation, differentiation, and survival of M2 macrophages

what drug can interact with this and what effect does it have?

Answer 15

the growth factor colony stimulating factor 1 (CSF1)

clodronate can interact with the CSF1 receptor, blocking binding sites with CSF1

Question 16

depletion of M2-polarized macrophages:

to improve the delivery efficiency of clondronate into the TAMs, ___ have been employed which can exhibit significant antitumor efficacy in various mouse models of colon cancer, glioma, and melanoma

Answer 16

nanoparticles like liposomal formulations

Question 17

depletion of TAMs (M2) by a novel liposomal clodronate (Clo-Lipo-DOTAP) inhibits ___ and ___ in melanoma

Answer 17

angiogenesis
tumor growth

passive targeting

Question 18

reprogramming of M2 macrophages into M1:

developed a biodegradable polymeric NP encapsulating two mRNAs which can encode M1-polarizing transcription factors: ___ and ___

this therapy has been successful in treating ___ cancer

Answer 18

interferon regulatory factor 5 (IRF5)

kinase beta (IKKbeta)

metastatic ovarian

Question 19

transforming TAMs into ___ cells using mRNA nanoparticles

what receptor involved and what kind of targeting?

Answer 19

tumoricidal cells

marcophage mannose receptor 1 (MRC1)
active targeting

Question 20

___ cancer is the second leading cause of cancer death among women worldwide

what are current treatments?

Answer 20

cervical

surgery, radiation, and chemo represent invasive and aggressive interventions (new strategies needed)

Question 21

the majority of cervical cancer cases are associated with persistent infections of ___

Answer 21

HPV-16

Question 22

DNA cervical cancer vaccines

Answer 22

engineered DNA –> oncoproteins –> antibodies oncoproteins (E7) –> immune response

Question 23

advantages of DNA vaccines over traditional vaccines

Answer 23

• stronger immune response
• can encode the info to produce several “antigens” including protein from cancer cells and diff types of HPV virus
• long-term cellular immunity
• cheaper
• easier to store (DNA very stable)
• FASTER TO DEVELOP & PRODUCE

Question 24

DNA vaccine delivery using ____ (peptide NPs)

Answer 24

BAPCs

Question 25

DNA-vaccine interacts with BAPCs through ___ interactions (wrapping around the ___ surface of the nanocapsules)

Answer 25

electrostatic
positive

Question 26

HPV-16

___ is an early protein, necessary for the induction and maintenance of the state of cellular malignancy

Answer 26

E7

Question 27

the goal of cancer vaccines is to achieve ___ or ___ immunity, as well as via ___ immunity

Answer 27

antigen-specific humoral
cell-mediated
innate

Question 28

describe the TC-1 cell transplantation model in mice

Answer 28

1- vaccine formulation: diff formulations of BAPCs-DNA complexes

–>3 days later, mice (C57BL/6) were injected subcutaneously with TC-1 cell epithelial lung cells expressing the E7 oncoprotein

3- tumor growth was checked by visual inspection and palpation three times per week for 70 days (animals were scored as tumor-bearing 2mm)

Question 29

what were the results of the mice immunized with BAPCs-DNA nanoparticles

Answer 29

after 30 days of the T-cell transplantation, only 2/15 mice showed a tumor (85% were protected)