A Phase I Clinical Trial Assessing the Safety, Feasibility and Immunologic Correlates of Allogeneic HPV-specific Cluster of Differentiation 4 (CD4)+ T Cells in Advanced HPV16-associated Malignancies

In this study, haploidentical relatives of a patient with recurrent or metastatic HPV 16-associated malignancy will be vaccinated with a therapeutic human papillomavirus (HPV) vaccine series to generate HPV-specific leukocytes. The cancer patient with recurrent or metastatic HPV16+ cancer will then be randomized to one of two arms: 1) non-myeloablative allogeneic bone marrow transplant or 2) cluster of differentiation 8 (CD8)-depleted donor lymphocyte infusion.

Start Date18 Oct 2023

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

[+1]

NCT04398524

/ Unknown statusPhase 2

A Phase II Study of Cemiplimab, an Anti-PD-1 Monoclonal Antibody, and ISA101b Vaccine in Patients With Recurrent/Metastatic HPV16 Positive Oropharyngeal Cancer Who Have Experienced Disease Progression With Prior Anti-PD-1 Therapy

This will be an open-label, phase 2 study in which subjects will receive ISA101b and cemiplimab.

Start Date01 Jul 2021

Sponsor / Collaborator

ISA Pharmaceuticals BV

[+1]

100 Clinical Results associated with ISA-101

100 Translational Medicine associated with ISA-101

100 Patents (Medical) associated with ISA-101

Literatures (Medical) associated with ISA-101

01 Jul 2025·ANNALS OF INTERNAL MEDICINE

Screening for Anal Cancer Among Men Who Have Sex With Men With HIV: Benefits, Harms, and Cost-Effectiveness Analyses

Article

Author: Nyitray, Alan G. ; Clifford, Gary M. ; Giuliano, Anna R. ; Meissner, Eric G. ; Gaisa, Michael ; Chiao, Elizabeth Y. ; Lazenby, Gweneth ; Palefsky, Joel M. ; Wentzensen, Nicolas ; Damgacioglu, Haluk ; Stier, Elizabeth ; Clarke, Megan A. ; Goldstone, Stephen E. ; Ortiz, Ana Patricia ; Sigel, Keith ; Deshmukh, Ashish A. ; Liu, Yuxin ; Lin, Yueh-Yun ; Chhatwal, Jagpreet ; Sonawane, Kalyani ; Jay, Naomi

BACKGROUND:

Following the success of the ANCHOR (Anal Cancer-HSIL Outcomes Research) trial, the U.S. Department of Health and Human Services recommends anal cancer screening for high-risk persons, particularly men who have sex with men (MSM) with HIV.

OBJECTIVE:

To quantify the cost-effectiveness and benefits versus harms of different anal cancer screening strategies.

DESIGN:

Microsimulation model.

DATA SOURCES:

The ANCHOR trial and published literature.

TARGET POPULATION:

MSM with HIV.

TIME HORIZON:

Lifetime.

PERSPECTIVE:

Health care sector.

INTERVENTION:

Cytology alone and human papillomavirus (HPV) testing (high-risk HPV [hrHPV], HPV16/18, and HPV16), co-testing, and triage options; ages at which to begin screening (≥35, ≥40, or ≥45 years); screening interval (annual, biennial, triennial, or quadrennial).

OUTCOME MEASURES:

Incremental cost-effectiveness ratios (ICERs) of dollars per quality-adjusted life-year (QALY) and the tradeoff of harms (high-resolution anoscopies [HRAs]) versus benefits (cancer cases averted and life-years gained).

RESULTS OF BASE-CASE ANALYSIS:

Screening initiation at age 35 years or older using cytology dominated initiation at ages 40 and 45 years or older, with ICERs ranging from $87 731 for a quadrennial interval to $350 100 for an annual interval. In the comparative analysis, the following unique strategies were on the cost-effectiveness frontier: quadrennial HPV16, quadrennial HPV16/18, triennial HPV16/18, triennial hrHPV, biennial HPV16/18, biennial hrHPV, annual cytology with hrHPV triage, and annual hrHPV; ICERs ranged from $81 341 to $2 510 847. In the harm-to-benefit analysis, triage options offered the most efficient HRA use.

RESULTS OF SENSITIVITY ANALYSIS:

ICERs decreased for newly eligible persons. For 35-year-old newly eligible MSM with HIV, ICERs for cytology ranged from $70 750 (quadrennial) to $223 895 (annual).

LIMITATION:

Findings are not generalizable to other high-risk populations.

CONCLUSION:

Anal cancer screening among MSM with HIV aged 35 years or older is cost-effective, but value-based prioritization of strategies is needed to optimize screening use.

PRIMARY FUNDING SOURCE:

National Cancer Institute.

13 Oct 2023·Clinical cancer research : an official journal of the American Association for Cancer Research

Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of High-Grade Anal Intraepithelial Neoplasia in HIV+ Men

Article

Author: de Vries, Henry J.C. ; Gosens, Karien C.M. ; Melief, Cornelis J.M. ; Welters, Marij J.P. ; Prins, Jan M. ; Boekestijn, Sanne ; Krebber, Wilhelmus J.T.A. ; van Noesel, Carel J.M. ; Loof, Nikki M. ; Richel, Olivier ; van der Wal, Allard C. ; van der Burg, Sjoerd H. ; Quint, Wim G.V.

Abstract:

Purpose::

Anal cancer is increasing in HIV+ men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I to II dose-finding study, we assessed the safety and efficacy of the human papillomavirus type 16 (HPV16) synthetic long peptide vaccine (SLP-HPV-01) in HIV+ MSM with HPV16-positive HGAIN.

Patients and Methods::

Four dosage schedules (1-5-10; 5-10-20; 10-20-40; and 40-40-40-40 μg) of SLP-HPV-01 were administered intradermally with a 3-week interval in 10 patients per dose level (DL). In each dose group, 5 patients also received 1 μg/kg pegylated IFNα-2b subcutaneously. Primary endpoints were safety and regression of HGAIN at 3, 6, and 12 months.

Results::

Eighty-one of 134 screened patients (60%) had HPV16-negative HGAIN lesions, leaving 53 eligible patients. Thirteen patients were excluded, leaving 40 men. The vaccine was well tolerated. One patient developed a generalized rash. The highest dosage level induced the strongest immune responses. There was no indication for stronger reactivity in the IFNα groups. Up to 18 months of follow-up, 8/38 intention-to-treat patients had a complete clinical and histologic response and one had a partial response (in total 9/38, 23.7%). At the highest dosage level, the clinical response was 4/10 (40%). Stronger immune responses were detected among clinical responders.

Conclusions::

The highest DL is safe, immunogenic, and associated with clinical responses to HPV16-induced lesions. However, as the majority of HGAIN is caused by the other HPV types, further studies should aim at pan-HPV vaccination to prevent or treat HGAIN.

01 Feb 2022·Journal for immunotherapy of cancerQ2 · MEDICINE

ISA101 and nivolumab for HPV-16⁺ cancer: updated clinical efficacy and immune correlates of response

Q2 · MEDICINE

ArticleOA

Author: Glisson, Bonnie S ; William, William ; Curran, Michael A ; Feng, Lei ; Wang, Qi ; Lee, Jack ; Johnson, Faye M ; Wang, Jing ; Sousa, Luana Guimaraes de ; Massarelli, Erminia ; Melief, Cornelis J M ; Ferrarotto, Renata ; Chin, Renee L ; Barrese, Tomas Z ; Rajapakshe, Kimal ; Coarfa, Cristian ; Wistuba, Ignacio ; Rodriguez Canales, Jaime

Background:

The combination of ISA101, a human papilloma virus (HPV) 16 peptide vaccine, and nivolumab showed a promising response rate of 33% in patients with incurable HPV-16+ cancer. Here we report long-term clinical outcomes and immune correlates of response.

Methods:

Patients with advanced HPV-16+ cancer and less than two prior regimens for recurrence were enrolled to receive ISA101 (100 µg/peptide) on days 1, 22, and 50 and nivolumab 3 mg/kg every 2 weeks beginning day 8 for up to 1 year. Baseline tumor samples were stained with multiplex immunofluorescence for programmed death-ligand 1 (PD-L1), programmed cell death protein-1 (PD-1), CD3, CD8, CD68, and pan-cytokeratin in a single panel and scanned with the Vectra 3.0 multispectral microscope. Whole transcriptome analysis of baseline tumors was performed with Affymetrix Clariom D arrays. Differential gene expression analysis was performed on responders versus non-responders.

Results:

Twenty-four patients were followed for a median of 46.5 months (95% CI, 46.0 months to not reached (NR)). The median duration of response was 11.2 months (95% CI, 8.51 months to NR); three out of eight (38%) patients with objective response were without progression at 3 years. The median and 3-year overall survival were 15.3 months (95% CI, 10.6 months to 27.2 months) and 12.5% (95% CI, 4.3% to 36%), respectively. The scores for activated T cells ((CD3+PD-1+)+(CD3+CD8+PD-1+)), activated cytotoxic T cells (CD3+CD8+PD-1+), and total macrophage ((CD68+PD-L1−)+(CD68+PD-L1+)) in tumor were directly correlated with clinical response (p<0.05) and depth of response with the two complete response patients having the highest degree of CD8+ T cells. Gene expression analysis revealed differential regulation of 357 genes (≥1.25 fold) in non-responders versus responders (p<0.05). Higher expression of immune response, inflammatory response and interferon-signaling pathway genes were correlated with clinical response (p<0.05).

Conclusions:

Efficacy of ISA101 and nivolumab remains promising in long-term follow-up. Increased infiltration by PD-1+ T cells and macrophages was predictive of response. Enrichment in gene sets associated with interferon-γ response and immune infiltration strongly predicted response to therapy. A randomized trial is ongoing to test this strategy and to further explore correlates of immune response with combined nivolumab and ISA101, versus nivolumab alone.

Trial registration number:

NCT02426892.

News (Medical) associated with ISA-101

03 Apr 2025

·frederick.cancer.gov

One shot of HPV vaccine protects long-term against cervical cancer

Women should be safe from cancer-causing human papilloma virus (HPV) for at least 20 years and probably more after just one dose of vaccine instead of the usual two or three, according to a study that further demonstrates the long-term effectiveness of a single dose. When first approved by the Food and Drug Administration nearly 20 years ago, vaccines against cancer-causing HPV were scheduled in three doses for adequate protection. But the cost and logistics of giving three shots, particularly in remote or underserved regions, can make it difficult to complete the full regimen. The new study pulled data from the ongoing Costa Rica HPV Vaccine Trial, which provided initial evidence that one dose of the bivalent HPV vaccine protected against HPV-16/18 infections. Researchers wanted to see how durable that protection was, because early on scientists observed that antibody responses from three vaccine doses were about four times higher than those from just one dose. So, they examined data from 500 of the Costa Rica trial participants. These included a group who had received three vaccine doses and a separate group aged 18 to 25 who got a single dose. All had agreed to follow-up visits 11, 14, and 16 years after vaccination.  The researchers gauged antibody levels against HPV-16 and HPV-18 at 11 and 16 years post-vaccination and reported in the Journal of the National Cancer Institute Monographs that antibody levels declined a bit over five years – with the three-dose levels declining faster. But HPV-16 and HPV-18 antibody seropositive rates from both dosing regimens "remained exceedingly high 16 years after vaccination." "Given the one-dose levels observed at 16 years, we project that women will have adequate antibody levels for much longer after vaccination with the bivalent HPV vaccine," the scientists reported. “Therefore, our study lends additional support to the World Health Organization recommendation of using a single-dose HPV vaccine schedule in immunization programs worldwide.” The current research was led by the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), with collaborators Ligia Pinto, Ph.D., and Troy Kemp, Ph.D., of the Frederick National Laboratory for Cancer Research where all antibody testing was done; Doug Lowy, M.D., of NCI; and scientists from both Agencia Costarricense de Investigaciones Biomédicas, in San José, Costa Rica, and Information Management Services in Maryland. Mary Ellen Hackett Manager, Communications Office 301-401-8670

VaccineClinical ResultClinical Study

13 May 2024

·www.prnewswire.com

SCG Cell Therapy Presented New Preclinical Data in an Oral Presentation at ASGCT 2024 Annual Meeting Highlighting Superior Tumor Inhibition of its Immunoswitch Armored HPV-TCR T Cell Therapy (SCG142) against a Broad Range of HPV-associated Cancers

SINGAPORE, May 12, 2024 /PRNewswire/ -- SCG Cell Therapy Pte Ltd (SCG), a clinical-stage biotechnology company developing novel immunotherapies for infectious diseases and their associated cancers, announced first preclinical data of its novel human papillomavirus (HPV)-specific T cell receptor-engineered T (TCR T) cell therapy armored with an TGFβRII-41BB immunoswitch – SCG142 – in an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting in Baltimore, Maryland. In preclinical studies, SCG142 demonstrated superior CD8+ and CD4+ TCR T cell proliferation and tumor inhibition both in-vitro and in-vivo compared to conventional TCR T without immunoswitch, including tumor rechallenge models. Importantly, SCG142 functionality is CD8 co-receptor independent, transferring desired effector functions also to CD4+ T cells and promoting longer persistence and improved proliferation of T cells. In addition, SCG142 exhibited high functional avidity and can recognize both genotypes HPV-16 and HPV-52, with a favorable safety profile with no alloreactivity or off-target toxicity in relevant toxicology models. "SCG142 is a novel and differentiated HPV-specific TCR T cell therapy with preclinical efficacy in various tumor types with expression of HPV-16- and HPV-52 genotypes. We're excited to demonstrate that armoring the TCR-T cells with the chimeric switch receptor didn´t change the favorable safety profile but helped to overcome the immune inhibitory signal of TGF-β, which can be crucial for effective treatment of solid tumors", said Dr. Susanne Wilde, Head of Preclinical Research of SCG Cell Therapy. "These promising results underscore the potential of SCG142 to provide new solutions for patients in a variety of HPV-16- and HPV-52 expressing cancers. Based on these encouraging data, we are eagerly advancing SCG142 towards clinical trials", she added. About SCG142 SCG142, an autologous HPV-specific TCR T cell therapy holding the promise as the best-in-class product. Utilizing SCG's proprietary GianTCRTM technology, high affinity and high avidity natural TCRs can be isolated to target against intracellular antigens presented through major histocompatibility complex (MHC) in solid tumors. Study results showed that SCG142, a fully natural HPV specific TCR armoured with chimeric switch receptor, has the potential to specially target HPV-16 and HPV-52-positive tumor cells in various HPV-related tumor types, generating CD8 co-receptor independent T cell functionality and sustained anti-tur activity. About Human Papillomavirus and Cancers Human papillomavirus (HPV) infection is the most common sexually transmitted infection. Nearly all sexually active people are infected with HPV and around half of these infections occur with a high-risk HPV type, which can lead to cancer development.1 As such, HPV infection accounts for more than 90% of anal and cervical cancers, about 70% of vaginal and vulvar cancers, and 60% of penile and oropharyngeal cancers, and it causes an estimated 630,000 cancers worldwide each year2x. About SCG Cell Therapy SCG is a leading biotechnology company focusing on the development of novel immunotherapies in infections and its associated cancers. The company targets the most common cancer-causing infections: helicobacter pylori, HPV, HBV and EBV, and develops a broad and unique pipeline of TCR-based cellular immunotherapy products against infection- associated cancers. With the proprietary GianTCRTM TCR screening platform, in house viral vector production and AutoCellTM, a fully closed and automatic cell therapy manufacturing system, the company covers the entire value chain from new target research and discovery, manufacturing, and clinical development. For more information about SCG, please visit us at . [1] HPV and cancer. National Cancer Institute. (2023, October 18) [2] Basic information about HPV and cancer. Centers for Disease Control and Prevent (2023, September 12) SOURCE SCG Cell Therapy Pte Ltd

Cell TherapyImmunotherapyClinical ResultAACRASCO

17 Apr 2024

·www.pharmaceutical-technology.com

Ultimovacs downsizes to funnel funds to cancer vaccine programme

Ultimovac’s UV1 works by inducing T cell response against telomerase reverse transcriptase (hTERT) – a protein that provides the limitless self-renewal hallmark in cancer progression. Image Credit: CI Photos / Shutterstock. Ultimovacs has implemented cash-saving strategies, including a 40% workforce reduction, to extend its reserves into Q4 2025. The operational adjustments are expected to provide a cash runway beyond the anticipated top-line readout from the next two Phase II trials – the FOCUS trial in Q3 this year, and the DOVACC trial in H1 2025. The UV1 cancer vaccine development programme has suffered some setbacks. The company has reported topline data from two Phase II trials, NIPU and INITIUM, for the vaccine used in combination with PD1 inhibitors in two cancer indications, with both trials failing to meet primary endpoints. The Phase II NIPU trial (NCT04300244) evaluated UV1 in combination with Bristol Myers Squibb’s checkpoint inhibitors Opdivo (nivolumab) and Yervoy (ipilimumab) as a second-line treatment in mesothelioma patients. The study failed to meet its primary endpoint of progression-free survival (PFS). The Phase II INITIUM trial (NCT02275416) also evaluated the UV1, Opdivo and Yervoy combination but in patients with unresectable or metastatic malignant melanoma. The study also failed to meet primary endpoints, with the company deciding to stop pursuing the therapy in this indication. See Also: NIH team develops AI tool to predict cancer drug response SGN-1 by Guangzhou Huajin Pharmaceutical Technology for Peritoneal Cancer: Likelihood of Approval Despite this, Ultimovacs expects positive readouts from the next two trials. The Phase II FOCUS trial (NCT05075122) evaluates the combination treatment of UV1 vaccine with MSD’s Keytruda (pembrolizumab) as a first-line treatment in patients with PD-L1 positive head and neck squamous cell carcinoma. The combination has been successful in the Phase I trial (NCT03538314), with an observed 67% overall survival rate at a three-year follow-up. While the company expects positive data in Q3 this year, it is prepared to wait for data readout from the DUVACC trial before deciding on the fate of UV1 should the FOCUS trial fail, said Ultimovac’s CEO Carlos de Sousa in a business update webcast today. The Phase II DUVACC trial (NCT04742075) evaluates UV1 in combination with AstraZeneca’s checkpoint inhibitor Infinzi (duvalumab) and Lynparza (olaparib), a poly-ADP ribose polymerase (PARP) inhibitor, as a second line treatment in patients with BRCA negative ovarian cancer. The trial is currently recruiting patients, with 40% of the total expected enrolment completed as of Q4 2023. UV1 is also being evaluated in an investigator-led Phase II LUNGVAC trial (NCT05344209). The study investigates the combination therapy of UV1 and Sanofi and Regeneron’s Libtayo (cemiplimab) as a first-line therapy in patients with advanced or metastatic non-small cell lung cancer. The trial started recruitment in October 2022 and reached only 15% enrolment as of Q4 2023. The topline data from the trial is expected in H1 2026. GlobalData forecasts therapeutic cancer vaccines as the weakest immuno-oncology agent class with relatively low global sales of up to $4bn by 2028, compared to checkpoint modulators sales reaching $120bn by 2028. GlobalData is the parent company of Pharmaceutical Technology . Other cancer vaccines in development include Transgene and Japanese NEC Corporation’s cancer vaccine, TG4050 , for the treatment of head and neck cancers and ISA Pharmaceuticals’ cancer vaccine, ISA101b , for treating oropharyngeal cancer.

Phase 2VaccineClinical ResultPhase 1

100 Deals associated with ISA-101

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
HPV16 Infection	Phase 2	Netherlands	Regeneron Pharmaceuticals, Inc.	22 Feb 2021
Human Papillomavirus-Related Squamous Cell Carcinoma	Phase 2	United States	Merck Sharp & Dohme Corp.	06 Jul 2020
Human Papillomavirus-Related Squamous Cell Carcinoma	Phase 2	United States	ISA Pharmaceuticals BV	06 Jul 2020
Squamous Cell Carcinoma of Head and Neck	Phase 2	United States	ISA Pharmaceuticals BV	06 Jul 2020
Squamous Cell Carcinoma of Head and Neck	Phase 2	United States	Merck Sharp & Dohme Corp.	06 Jul 2020
HPV16 positive Oropharyngeal Cancer	Phase 2	United States	Pfizer Inc.	04 Apr 2018
HPV16 positive Oropharyngeal Cancer	Phase 2	United States	ISA Pharmaceuticals BV	04 Apr 2018
Lip Neoplasms	Phase 2	United States	ISA Pharmaceuticals BV	04 Apr 2018
Lip Neoplasms	Phase 2	United States	Pfizer Inc.	04 Apr 2018
HPV16 positive solid tumors	Phase 2	United States	Bristol Myers Squibb Co.	23 Dec 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04646005 (CTgov)	Phase 2	Recurrent Cervical Cancer	113	ISA 101b+Cemiplimab	vgtrkqxfxk = dzmvehczzt uctnrdxrkq (dxvodhfxag, ihiukdxzot - kcykovokcl) View more	-	19 Sep 2024
NCT04646005 (ASCO2024) Manual	Phase 2	Uterine Cervical Cancer Second line PD-L1	113	Cemiplimab 350 mgISA101b	jydexpwxte(eiohnslycj) = jjaaxapyms fvirsmyqvw (ypmisnhowa, 9.9 - 23.7) View more	Positive	24 May 2024
NCT03669718 (OpcemISA, ASCO2024)	Phase 2	HPV16 positive Oropharyngeal Cancer HPV16-positive	198	ISA101b + cemiplimab	lccitvywxp(hwijxftcws) = niqygrhxvv roerygwflv (yatvocpjwv ) View more	Positive	24 May 2024
NCT03669718 (OpcemISA, ASCO2024)	Phase 2	HPV16 positive Oropharyngeal Cancer HPV16-positive	198	Placebo + cemiplimab	lccitvywxp(hwijxftcws) = ubzcxlccma roerygwflv (yatvocpjwv ) View more	Positive	24 May 2024
NCT03669718 (OpcemISA , PRNewswire) Manual	Phase 2	Oropharyngeal Neoplasms	199	ISA101b+Cemiplimab	ddpvkaxrud(tqjjtfbvsh) = not meet in the entire population ugzyeonldo (kegmusmudf ) Not Met View more	Negative	12 Dec 2023
NCT03669718 (OpcemISA , PRNewswire) Manual	Phase 2	Oropharyngeal Neoplasms	199	Placebo+Cemiplimab		Negative	12 Dec 2023
NCT04398524 (ASCO 12023 \| ASCO 22023) Manual	Phase 2	HPV16 positive Oropharyngeal Cancer Second line HPV16 Positive	26	ISA101b 100µg/peptide+cemiplimab 350mg	iyxyjukasn(sxrbkmcnhp) = eeqvgjacot houzhrsiif (mamcnzjekn ) View more	Positive	31 May 2023
NCT02426892 (CTgov)	Phase 2	Squamous Cell Carcinoma of the Oropharynx \| Solid tumor \| HPV16 positive solid tumors	33	ISA101 Vaccine+Nivolumab	tdvquioses = xwelxfxrbn sljmozajhs (favcasdffg, binngeriaj - kkhyhwpgez) View more	-	18 Apr 2023
NCT03258008 (CTgov)	Phase 2	HPV16 positive Oropharyngeal Cancer \| Lip Neoplasms	3	Utomilumab	phjhvlwgki = yecsrkecdb itkmmjmkhe (nntnqwgepk, rnnxupmyvu - vobouxbyvt) View more	-	16 Dec 2022
NCT02426892 (Pubmed \| J Immunother Cancer) Manual	Phase 2	HPV16 Infection HPV-16 positive	24	Nivolumab+ISA 101	icocdqtbfa(cepfpgjwlg) = padnwdciat stvqtljfuy (kzyqzwogmr ) View more	Positive	01 Feb 2022
NCT02128126 (Pubmed \| Sci Transl Med) Manual	Phase 1/2	Neoplasms	72	ISA 101	tqbqwiyiji(uifidisjny) = dehnnuwwyd wtixoaldzf (jlmajigkcp )	Positive	18 Mar 2020
SITC2018	Phase 2	HPV16 Infection CD3+CD8+PD-1+ \| CD68+PD-L1- \| CD68+PD-L1+ ... View more	24	ISA101	hoftwbhcmc(xigndaylyf) = mcfnksqsdb xmerbcbiin (fzzoyxsrga ) View more	Positive	06 Nov 2018

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