Paige Krystofinski
A5014330732- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Virus-based gene therapy research
- Reproductive System and Pregnancy
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Wound Healing and Treatments
- Ferroptosis and cancer prognosis
- Genetic factors in colorectal cancer
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- Melanoma and MAPK Pathways
- Pressure Ulcer Prevention and Management
- Dermatologic Treatments and Research
- Hair Growth and Disorders
- Burn Injury Management and Outcomes
- Fungal Biology and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Biomedical Ethics and Regulation
University of California, Los Angeles
2016-2021
UCLA Jonsson Comprehensive Cancer Center
2018-2019
APLA Health
2017-2018
Parker Institute for Cancer Immunotherapy
2018
UCLA Health
2017
Abstract To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 cancer primary tumor samples, including 179 classified as microsatellite instability–high (MSI-high). This set includes The Cancer Genome Atlas cohort 592 completed here. MSI-high, a hypermutated, immunogenic subtype had high rate significantly mutated genes important immune-modulating pathways antigen presentation machinery, biallelic losses B2M HLA due to copy-number...
Mechanism-based strategies to overcome resistance PD-1 blockade therapy are urgently needed. We developed genetic acquired resistant models of JAK1, JAK2, and B2M loss-of-function mutations by gene knockout in human murine cell lines. Human melanoma lines with JAK1/2 became insensitive IFN-induced antitumor effects, while was no longer recognized antigen-specific T cells hence cytotoxicity. All these led anti-PD-1 vivo. JAK1/2-knockout could be the activation innate adaptive immunity...
Abstract Interleukin-2 (IL-2) is a component of most protocols adoptive cell transfer (ACT) therapy for cancer, but limited by short exposure and high toxicities. NKTR-214 kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported increases the proliferation, homing persistence anti-tumor T cells compared with IL-2, superior antitumor...
BRAF inhibitors are highly effective therapies for the treatment of BRAF(V600)-mutated melanoma, with main toxicity being a variety hyperproliferative skin conditions due to paradoxical activation mitogen-activated protein kinase (MAPK) pathway in wild-type cells. Most these changes improve when MEK inhibitor is co-administered, as it blocks MAPK activation. Here we show how vemurafenib accelerates wound healing by inducing proliferation and migration human keratinocytes through...
Wound healing is a multi-step process to rapidly restore the barrier function. This often impaired in diabetic patients resulting chronic wounds and amputation. We previously found that paradoxical activation of mitogen-activated protein kinase (MAPK) pathway via topical administration BRAF inhibitor vemurafenib accelerates wound by activating keratinocyte proliferation reepithelialization pathways healthy mice. Herein, we investigated whether this acceleration also occurs not only improves...
To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a trial to transplant genetically-modified hematopoietic stem (HSCs) together with adoptive cell transfer both engineered express an NY-ESO-1 TCR. Here, report the preclinical studies performed enable investigational new drug (IND) application.HSCs transduced lentiviral vector expressing TCR PET reporter/suicide gene HSV1-sr39TK retroviral were coadministered...
This article decries a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences at specific sites in the genomes primary human T cells, while preserving cell viability function.
Abstract The adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) has been shown to induce effective anti-tumor response. However, tumors frequently relapse after an initial Another strategy towards stimulating the immune system is use high-dose interleukin-2 (IL-2) target IL-2 receptor (IL2R), leading expansion. clinically approved expands both tumor-killing CD8+ effector (CD8T) as well regulatory (Tregs) through binding IL-2Rβγ...
<p>Supplemental Figure 1: Hypothetical model of peripheral blood TCR-transgenic cell repopulation. Supplemental 2: GLP team organizational chart. 3. Bone marrow transplant (BMT) optimization studies in HLA-A2/Kb transgenic mice. 4. Body weight and hematology assessment at day 5 3 months after BMT. 5. Spleen bone cellularity 6. Serum chemistry 7. Flow cytometry gating strategy for splenocytes phenotype characterization. 8. Survival BMT with Lin- cells transduced LV-empty, LV-NY-ESO-1...
<div>AbstractPurpose:<p>To improve persistence of adoptively transferred T-cell receptor (TCR)–engineered T cells and durable clinical responses, we designed a trial to transplant genetically-modified hematopoietic stem (HSCs) together with adoptive cell transfer both engineered express an NY-ESO-1 TCR. Here, report the preclinical studies performed enable investigational new drug (IND) application.</p>Experimental Design:<p>HSCs transduced lentiviral vector...
<div>AbstractPurpose:<p>To improve persistence of adoptively transferred T-cell receptor (TCR)–engineered T cells and durable clinical responses, we designed a trial to transplant genetically-modified hematopoietic stem (HSCs) together with adoptive cell transfer both engineered express an NY-ESO-1 TCR. Here, report the preclinical studies performed enable investigational new drug (IND) application.</p>Experimental Design:<p>HSCs transduced lentiviral vector...
<p>Supplemental Figure 1: Hypothetical model of peripheral blood TCR-transgenic cell repopulation. Supplemental 2: GLP team organizational chart. 3. Bone marrow transplant (BMT) optimization studies in HLA-A2/Kb transgenic mice. 4. Body weight and hematology assessment at day 5 3 months after BMT. 5. Spleen bone cellularity 6. Serum chemistry 7. Flow cytometry gating strategy for splenocytes phenotype characterization. 8. Survival BMT with Lin- cells transduced LV-empty, LV-NY-ESO-1...
<div>Abstract<p>To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 cancer primary tumor samples, including 179 classified as microsatellite instability–high (MSI-high). This set includes The Cancer Genome Atlas cohort 592 completed here. MSI-high, a hypermutated, immunogenic subtype had high rate significantly mutated genes important immune-modulating pathways antigen presentation machinery, biallelic losses...
<p>Supplementary Figures S1-S12 (with legends)</p>
<p>Supplementary Table S2: Somatic mutations</p>
<p>Supplementary Table S21: Segmented copy-number ratios</p>
<p>Supplementary Table S21: Segmented copy-number ratios</p>
<p>Supplementary Figures S1-S12 (with legends)</p>
<p>Supplementary Table S22: Segmented b-allele deficits</p>
<p>Supplementary Tables S16-S19, describing IHC results on NHS/HPFS data</p>
<div>Abstract<p>To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 cancer primary tumor samples, including 179 classified as microsatellite instability–high (MSI-high). This set includes The Cancer Genome Atlas cohort 592 completed here. MSI-high, a hypermutated, immunogenic subtype had high rate significantly mutated genes important immune-modulating pathways antigen presentation machinery, biallelic losses...
<p>Supplementary Tables S1, S3 through S15, S20, and S23</p>
<p>Supplementary Tables S1, S3 through S15, S20, and S23</p>
<p>Supplementary Table S22: Segmented b-allele deficits</p>