Killer cells can save us from chemo hell

The Sunday Telegraph (Sydney) - - NEWS - JANE HANSEN

TWO years af­ter Macken­zie Isedale be­gan her gru­elling jour­ney to beat leukaemia, the 11year-old last week rang the bell on her last chemo treat­ment.

The toxic med­i­ca­tion had left her bald, sick with painful ul­cers, in­ca­pac­i­tated for months and un­able to walk. For her mother Er­rin it was a night­mare to watch her pre­vi­ously bub­bly girl be­come so de­bil­i­tated in pur­suit of a cure.

“It was heart­break­ing, she went through a stage when she couldn’t walk for three months and to see your bouncy nineyear-old who loved gym­nas­tics to be stuck in a wheel­chair was aw­ful,” Mrs Isedale, from the small town of Welby in the South­ern High­lands, said.

“It was hard to ex­plain to her she had to get sicker to get bet­ter.”

But in a po­ten­tial “game chang­ing” trial to start soon out of the West­mead In­sti­tute of Med­i­cal Re­search, other children and adults may be spared hav­ing to en­dure such ex­cru­ci­at­ing and ex­haust­ing chemo­ther­apy treat­ment for acute lym­phoblas­tic leukaemia (ALL).

Rather than rounds of toxic chemo­ther­apy drugs de­signed to kill cancer cells, sci­en­tists will use the body’s own im­mune cells, called T cells, re-en­gi­neer­ing them to recog­nise and de­stroy cancer cells be­fore rein­tro­duc­ing them into the body.

Pae­di­atric on­col­o­gist Dr Lu­ciano Dalla-P ozza said the trial, which will re­cruit patients next month, had the po­ten­tial to lift sur­vival rates from the cur­rent 80 per cent to near 100 per cent.

“The cure rate with chemo­ther­apy is 80 per cent, but 20 per cent will need a bone-mar­row

trans­plant and only half of those will re­spond. The CAR-T cells will be tri­alled on the re­main­ing 10 per cent,” he said.

“There’s a clear prospect a lot more will be cured. That small group of children we fail, im­munother­apy seems to have an as­ton­ish­ing ef­fect and we hope that trans­lates to a cure.”

The treat­ment cured Emily White­head, a 12-year-old from the US who had failed all other treat­ments. Di­ag­nosed with ALL at age five, she re­lapsed twice despite ex­ten­sive rounds of chemo­ther­apy. A bone-mar­row trans­plant fell through at the last minute and in des­per­a­tion, her par­ents en­rolled her in a phase 1 CAR-T cell trial. At age seven, Emily be­came the first child to re­ceive the ther­apy at the Children’s Hos­pi­tal of Philadelphia. Her T cells were ex­tracted from her blood, “re­pro­grammed” and mul­ti­plied in the lab to target and com­bat her cancer. This army of “hunter” T-cells was then in­fused back into her body.

She is now five years cancer free and her T cells are still work­ing to iden­tify any new cancer cells.

“That sin­gle suc­cess, when none was an­tic­i­pated, it was pie in the sky stuff, but to see that hap­pen and then re­in­forced with re­peated suc­cess is re­ally promis­ing,” Dr Dalla-Pozza said.

Early re­sults from clin­i­cal tri­als have reported 93 per cent of pae­di­atric patients with re­lapsed ALL have achieved re­mis­sion.

“T cells help pro­tect us from de­vel­op­ing cancer but cancer cells have de­vel­oped a way around de­tec­tion, the T cells don’t see the cancer. We put a new kind of re­cep­tor, like a key in a lock mech­a­nism, into the T cell so it can see the tu­mour cells,” Dr Ken Mick­leth­waite, group leader for CAR-T cells re­search at West­mead In­sti­tute of Med­i­cal Re­search, said.

The “key” is cre­ated with an an­ti­body that recog­nises the tu­mour and is com­bined with a new protein whose gene is then in­tro­duced to the pa­tient’s T cell, grown in the lab and in­fused back into the pa­tient.

“Hope­fully this will re­place chemo­ther­apy. I see a fu­ture where a pa­tient presents, has cells col­lected, has some chemo to shrink the tu­mour and af­ter one month given the CAR T cells and that is likely the only treat­ment they will need,” Dr Mick­leth­waite said.

Macken­zie, who is an am­bas­sador for the Children’s Cancer In­sti­tute’s “En­dure for a Cure” cam­paign, is now well but will need monthly blood tests to check for re­lapses.

Pic­ture: Ale Pho­tog­ra­phy

Macken­zie Isedale and her mum Er­rin af­ter fin­ish­ing her treat­ment.

Macken­zie (above) while in hos­pi­tal, and (right) play­ing foot­ball.

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